Descriptor: "MESH : Transcription, Genetic" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH : Transcription, Genetic"' showing total 44 results

Start Over Descriptor "MESH : Transcription, Genetic"

44 results on '"MESH : Transcription, Genetic"'

1. Cytokine and gene transcription profiles of immune responses elicited by HIV lipopeptide vaccine in HIV-negative volunteers

Author: Laura, Richert, Sophie, Hue, Hakim, Hocini, Mathieu, Raimbault, Christine, Lacabaratz, Mathieu, Surenaud, Aurélie, Wiedemann, Pascaline, Tisserand, Christine, Durier, Dominique, Salmon, Jean-Daniel, Lelièvre, Geneviève, Chêne, Rodolphe, Thiébaut, Yves, Lévy, C, Desaint, Statistics In System biology and Translational Medicine (SISTM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria) - Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP] - Assistance publique - Hôpitaux de Paris (AP-HP), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: CD4-Positive T-Lymphocytes, Male, Enzyme-Linked Immunospot Assay, Transcription, Genetic, MESH : Cytokines, medicine.medical_treatment, MESH : Enzyme-Linked Immunospot Assay, HIV Antibodies, Lymphocyte Activation, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], MESH: Lipopeptides, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interferon, Immunology and Allergy, MESH : Female, MESH: Double-Blind Method, 030212 general & internal medicine, MESH : HIV Seronegativity, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: HIV Seronegativity, AIDS Vaccines, MESH: Cytokines, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Middle Aged, MESH : Gene Expression Regulation, Immunogenicity, ELISPOT, Vaccination, MESH: CD4-Positive T-Lymphocytes, MESH : Adult, Middle Aged, MESH: Gene Expression Regulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Cytokine, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH : CD4-Positive T-Lymphocytes, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Female, Adjuvant, medicine.drug, Adult, MESH : AIDS Vaccines, MESH : Male, Immunology, Biology, Peripheral blood mononuclear cell, MESH : HIV Antibodies, Lipopeptides, 03 medical and health sciences, MESH : Lipopeptides, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, MESH: AIDS Vaccines, Immune system, Double-Blind Method, HIV Seronegativity, medicine, MESH : Double-Blind Method, Humans, MESH : Middle Aged, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH: Humans, MESH: HIV Antibodies, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, MESH: Adult, MESH: Vaccination, MESH: Male, MESH : Vaccination, Gene Expression Regulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, MESH: Enzyme-Linked Immunospot Assay, MESH: Female
Abstract: International audience; OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-γ, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.
Published: 2013
Full Text: View/download PDF

2. Genome sequence of Aedes aegypti, a major arbovirus vector

Author: Sergio Verjovski-Almeida, James E. Galagan, Ryan C. Kennedy, Zhiyong Xi, Jason R. Miller, Eric Eisenstadt, Kyanne R. Reidenbach, Robert V. Bruggner, Yu-Hui Rogers, Hadi Quesneville, Doreen Werner, Owen White, Alexander S. Raikhel, Mario Stanke, J. Spencer Johnston, Diane D. Lovin, Evgenia V. Kriventseva, Ian T. Paulsen, Kathryn S. Campbell, Norman H. Lee, Ewan Birney, Karyn Megy, Hean Koo, David Kulp, Shelby L. Bidwell, Jingsong Zhu, Philip Montgomery, Paolo Amedeo, Yongmei Zhao, Chinnappa D. Kodira, Javier Costas, Michael C. Schatz, Steven P. Sinkins, Claire M. Fraser-Liggett, Martin Shumway, Kurt LaButti, Akio Mori, Brendan J. Loftus, Manfred Grabherr, Eric O. Stinson, Frank H. Collins, Zhijian Jake Tu, Monique R. Coy, Matt Crawford, Janice P. Vanzee, William M. Gelbart, Joshua Orvis, Peter Arensburger, Chunhong Mao, Evgeny M. Zdobnov, Saul A. Kravitz, Suely Lopes Gomes, David DeCaprio, David G. Hogenkamp, Daniel Lawson, Dennis L. Knudson, David W. Severson, George Dimopoulos, Marcelo B. Soares, Sinéad B. O'Leary, Peter W. Atkinson, David M. Jaffe, Becky deBruyn, Martin Hammond, Ana L. T. O. Nascimento, Jim Biedler, Stefan Wyder, Jose M. C. Tubio, Bruce W. Birren, Catherine A. Hill, Chad Nusbaum, Eduardo Lee, Song Li, Susan E. Brown, Jennifer R. Wortman, James R. Hogan, Hamza El-Dorry, Qi Zhao, Linda Hannick, Carlos Frederico Martins Menck, Vishvanath Nene, Jonathan Crabtree, Steven L. Salzberg, Michael H. Holmes, Maria de Fatima Bonaldo, Quinghu Ren, Mihaela Pertea, Charles Roth, Evan Mauceli, Karin Eiglmeier, Horacio Naveira, Brian J. Haas, Qiandong Zeng, Neil F. Lobo, Jennifer R. Schneider, The Institute for Genomic Research, The Institute for Genomic Research, Rockville, European Bioinformatics Institute [Hinxton] ( EMBL-EBI ), European Molecular Biology Laboratory [Hinxton], Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Broad Institute of MIT and Harvard, Virginia Polytechnic Institute and State University [Blacksburg], University College Dublin [Dublin] ( UCD ), Bloomberg School of Public Health, Johns Hopkins University ( JHU ) -Bloomberg School of Public Health, University of Geneva Medical School, Swiss Institute of Bioinformatics-University of Geneva Medical School, University of Notre Dame ( UND ), Harvard University [Cambridge], College of Agricultural Sciences Colorado State University, Colorado State University [Fort Collins] ( CSU ) -College of Agricultural Sciences, Northwestern University [Evanston], University of California [Riverside] ( UCR ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), University of Oxford [Oxford], Purdue University [West Lafayette], Centro Nacional de Genotipado Fundación Pública Galega de Medicina Xenómica Hospital Clínico Universitario de Santiago, Centro Nacional de Genotipado-Fundación Pública Galega de Medicina Xenómica-Hospital Clínico Universitario de Santiago, Institut Pasteur [Paris], Universidade de Sao Paulo Instituto de Quimica, Universidade de São Paulo ( USP ) -Instituto de Quimica, Texas A&M University [College Station], Joint Technology Center, University of Massachusetts [Amherst] ( UMass Amherst ), Universidade de Sao Paulo, Institute of Biomedical Sciences, Universidade de São Paulo ( USP ) -Institute of Biomedical Sciences, Instituto Butantan [São Paulo], Universidade da Coruña, University of Maryland [College Park], Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University of California [Santa Cruz] ( UCSC ), Complexo Hospitalario Universitario de Santiago, Universität Göttingen, Georg-August-Universität Göttingen, George Washington University Medical Center, George Washington University ( GW ), The Institute for Genomic Research (TIGR), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University College Dublin [Dublin] (UCD), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL)-University of Geneva Medical School, University of Notre Dame [Indiana] (UND), Colorado State University [Fort Collins] (CSU)-College of Agricultural Sciences, University of California [Riverside] (UCR), University of California, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), Universidade de São Paulo (USP)-Instituto de Quimica, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Universidade de São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP), University of Maryland System, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of California [Santa Cruz] (UCSC), Georg-August-University [Göttingen], The George Washington University (GW), George Washington University (GW), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL)-University of Geneva Medical School, Harvard University, University of California [Riverside] (UC Riverside), University of California (UC), University of Oxford, Institut Pasteur [Paris] (IP), Universidade de São Paulo = University of São Paulo (USP)-Instituto de Quimica, Universidade de São Paulo = University of São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo = University of São Paulo (USP), University of California [Santa Cruz] (UC Santa Cruz), Georg-August-University = Georg-August-Universität Göttingen, Zdobnov, Evgeny, and Wyder, Stefan
Subjects: 0106 biological sciences, Male, Transcription, Genetic, Genome, Insect, transposons, receptors, Genes, Insect, Aedes/ genetics/metabolism, MESH: Genes, Insect, Yellow Fever/prevention & control/transmission, MESH: Base Sequence, 01 natural sciences, Dengue/prevention & control/transmission, MESH: Protein Structure, Tertiary, MESH: Arboviruses, MESH : Insect Vectors, MESH: Insect Proteins, MESH : Anopheles gambiae, MESH: Animals, MESH : Arboviruses, insects, MESH: Yellow Fever, superfamily, ddc:616, 0303 health sciences, Anopheles, MESH : Genes, Insect, 3. Good health, yellow-fever mosquito, anopheles-gambiae, drosophila-melanogaster, expression, evolution, organization, Drosophila melanogaster, MESH: DNA Transposable Elements, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Multigene Family, Public Health, MESH : Protein Structure, Tertiary, MESH: Sex Characteristics, Molecular Sequence Data, MESH : Multigene Family, MESH: Sex Determination (Genetics), MESH : Sex Determination (Genetics), Arbovirus, Article, 03 medical and health sciences, Species Specificity, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Anopheles gambiae, Yellow Fever, MESH: Species Specificity, Humans, MESH: Humans, MESH: Molecular Sequence Data, fungi, MESH : Humans, MESH : Sex Characteristics, Membrane Transport Proteins, Sex Determination Processes, medicine.disease, Insect Vectors, Protein Structure, Tertiary, Sex Determination (Genetics), MESH: Multigene Family, MESH: Female, MESH : Sequence Analysis, DNA, MESH: Sequence Analysis, DNA, Drosophila melanogaster/genetics, MESH : Molecular Sequence Data, Odorant binding, Insect Proteins/genetics, Anopheles gambiae, MESH: Dengue, Genome, MESH: Membrane Transport Proteins, Dengue, MESH : Membrane Transport Proteins, Aedes, Insect Vectors/ genetics/metabolism, MESH : Drosophila melanogaster, MESH : Female, Membrane Transport Proteins/genetics, Genetics, MESH : Insect Proteins, Sex Characteristics, Multidisciplinary, MESH: Synteny, MESH: Aedes, MESH : Genome, Insect, MESH : DNA Transposable Elements, Insect Proteins, Female, Orthologous Gene, MESH : Male, MESH : Dengue, Aedes aegypti, MESH: Insect Vectors, Biology, 010603 evolutionary biology, Synteny, MESH: Drosophila melanogaster, Protein Structure, Tertiary/genetics, MESH : Yellow Fever, parasitic diseases, medicine, MESH : Species Specificity, Animals, 030304 developmental biology, MESH : Aedes, Base Sequence, MESH: Genome, Insect, MESH: Transcription, Genetic, MESH : Synteny, MESH : Transcription, Genetic, Sequence Analysis, DNA, biology.organism_classification, MESH: Male, DNA Transposable Elements, MESH : Base Sequence, MESH : Animals, Arboviruses, Anopheles gambiae/genetics/metabolism
Abstract: We present a draft sequence of the genome of Aedes aegypti , the primary vector for yellow fever and dengue fever, which at ∼1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae . Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of ∼4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster . Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of ∼2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
Published: 2016
Full Text: View/download PDF

3. EWS-FLI1 inhibits TNFα-induced NFκB-dependent transcription in Ewing sarcoma cells

Author: Christian Auclair, Franck Tirode, Olivier Delattre, Alain Lilienbaum, Julie Lagirand-Cantaloube, Marie-Hélène Kryszke, Karine Laud, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Stress et pathologies du cytosquelette EA 300, Université Paris Diderot - Paris 7 (UPD7), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Oncogene Proteins, Fusion, Transcription, Genetic, Electrophoretic Mobility Shift Assay, MESH : Oncogene Proteins, Fusion, medicine.disease_cause, Biochemistry, 0302 clinical medicine, MESH: Transcription Factor RelA, Genes, Reporter, Transcription (biology), Gene expression, Luciferases, MESH : Tumor Necrosis Factor-alpha, 0303 health sciences, Gene knockdown, MESH: Proto-Oncogene Protein c-fli-1, MESH: Gene Expression Regulation, Neoplastic, MESH : Genes, Reporter, MESH: Bone Neoplasms, Gene Expression Regulation, Neoplastic, MESH: Sarcoma, Ewing's, MESH : Sarcoma, Ewing's, MESH : Electrophoretic Mobility Shift Assay, 030220 oncology & carcinogenesis, Tumor necrosis factor alpha, MESH: Cell Line, Tumor, MESH : Gene Expression Regulation, Neoplastic, Biophysics, Bone Neoplasms, Sarcoma, Ewing, Biology, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Transcription factor, MESH : Bone Neoplasms, 030304 developmental biology, MESH : Luciferases, MESH: Humans, Proto-Oncogene Protein c-fli-1, Tumor Necrosis Factor-alpha, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH : Transcription Factor RelA, MESH : Humans, MESH: Genes, Reporter, fungi, Transcription Factor RelA, MESH : Transcription, Genetic, Promoter, Cell Biology, Fusion protein, MESH : Proto-Oncogene Protein c-fli-1, MESH: Tumor Necrosis Factor-alpha, MESH: Electrophoretic Mobility Shift Assay, Cancer research, MESH: Luciferases, RNA-Binding Protein EWS, Carcinogenesis, MESH: Oncogene Proteins, Fusion
Abstract: International audience; Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NFkappaB) is a tightly regulated transcription factor controlling cell survival, proliferation and differentiation, as well as tumorigenesis. NFkappaB activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NFkappaB activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NFkappaB basal activity, but impairs TNF-induced NFkappaB-driven transcription, at least in part through inhibition of NFkappaB binding to DNA. We detected an in vivo physical interaction between the fusion protein and NFkappaB p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NFkappaB.
Published: 2010
Full Text: View/download PDF

4. Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia

Author: Bernard Mari, Elodie Portales-Casamar, Bruno Cassinat, Evelyne Friederich, Christine Chomienne, Khalil Arar, Pascal Barbry, Thomas Maurin, Anne Saumet, Manuella Bouttier, Laurent Vallar, Guillaume Vetter, Charles-Henri Lecellier, Wyeth W. Wasserman, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cytoskeleton and Cell Plasticity Lab, Université du Luxembourg (Uni.lu), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of British Columbia (UBC), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Public Santé, CRP-Santé Luxembourg, Sigma-Proligo, Granulopoiese et Processus Leucemiques (UMR_S_718), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université du Luxembourg ( Uni.lu ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), University of British Columbia ( UBC ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Granulopoiese et Processus Leucemiques, and Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Oncogene Proteins, Fusion, Transcription, Genetic, Retinoic acid, MESH : Leukemia, Promyelocytic, Acute, MESH : Oncogene Proteins, Fusion, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, MESH : Tumor Markers, Biological, MESH : Homeodomain Proteins, RNA, Neoplasm, MESH : Tretinoin, Regulation of gene expression, 0303 health sciences, Gene Expression Regulation, Leukemic, Myeloid leukemia, Hematology, MESH : Arsenic, 3. Good health, MESH : Antineoplastic Agents, Leukemia, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, MESH: Gene Expression Regulation, Leukemic, medicine.drug, Acute promyelocytic leukemia, MESH: Cell Line, Tumor, Immunology, Antineoplastic Agents, Tretinoin, Biology, MESH : Cell Adhesion Molecules, Arsenic, 03 medical and health sciences, Cell Line, Tumor, MESH: Arsenic, MESH: Homeodomain Proteins, microRNA, Biomarkers, Tumor, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Homeodomain Proteins, MESH: Tretinoin, MESH: Humans, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Cell Biology, MESH: RNA, Neoplasm, medicine.disease, MESH : MicroRNAs, MicroRNAs, MESH : RNA, Neoplasm, MESH : Gene Expression Regulation, Leukemic, chemistry, Retinoic acid receptor alpha, MESH: Tumor Markers, Biological, Cancer research, MESH: Antineoplastic Agents, Cell Adhesion Molecules, MESH: MicroRNAs, MESH: Leukemia, Promyelocytic, Acute, MESH: Oncogene Proteins, Fusion
Abstract: Micro(mi)RNAs are small noncoding RNAs that orchestrate many key aspects of cell physiology and their deregulation is often linked to distinct diseases including cancer. Here, we studied the contribution of miRNAs in a well-characterized human myeloid leukemia, acute promyelocytic leukemia (APL), targeted by retinoic acid and trioxide arsenic therapy. We identified several miRNAs transcriptionally repressed by the APL-associated PML-RAR oncogene which are released after treatment with all-trans retinoic acid. These coregulated miRNAs were found to control, in a coordinated manner, crucial pathways linked to leukemogenesis, such as HOX proteins and cell adhesion molecules whose expressions are thereby repressed by the chemotherapy. Thus, APL appears linked to transcriptional perturbation of miRNA genes, and clinical protocols able to successfully eradicate cancer cells may do so by restoring miRNA expression. The identification of abnormal miRNA biogenesis in cancer may therefore provide novel biomarkers and therapeutic targets in myeloid leukemias.
Published: 2009
Full Text: View/download PDF

5. Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-α Expression in Breast Cancer Cells

Author: Robert Barouki, Etienne Blanc, Nathalie M. Mazure, Fabrice Lecuru, Marie-Claude Fulchignoni-Lataud, Marie-Aude Le Frere Belda, Anne Dreiem, Thérèse Hervèe Mayi, Charbel Massaad, Vincent Favaudon, Liliane Massaad-Massade, Ramzi Seifeddine, Laboratoire de Détection et de Géophysique (CEA) (LDG), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), IFR50, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Paris-Sud, Université Paris-Sud - Paris 11 (UP11), Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Détection et de Géophysique (CEA) ( LDG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Régulation de la transcription et maladies génétiques ( RTMG ), Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Faculté de Médecine Nice, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie
Subjects: Cancer Research, Hypoxia-Inducible Factor 1, MESH : Molecular Sequence Data, MESH : RNA, Messenger, Transcription, Genetic, MESH : Immunohistochemistry, MESH: Cell Hypoxia, Electrophoretic Mobility Shift Assay, MESH: Cell Cycle, RNA polymerase II, MESH : Blotting, Western, MESH : Breast Neoplasms, MESH: Base Sequence, MESH : RNA, Small Interfering, MESH: Down-Regulation, MESH : Down-Regulation, 0302 clinical medicine, Transcription (biology), MESH: Reverse Transcriptase Polymerase Chain Reaction, Enhancer binding, MESH: RNA, Small Interfering, Gene expression, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH : CCAAT-Enhancer-Binding Protein-alpha, RNA, Small Interfering, Promoter Regions, Genetic, 0303 health sciences, Gene knockdown, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, MESH : Reverse Transcriptase Polymerase Chain Reaction, Immunohistochemistry, Cell Hypoxia, 3. Good health, MESH: Promoter Regions (Genetics), Oncology, MESH : Electrophoretic Mobility Shift Assay, 030220 oncology & carcinogenesis, MESH: Cell Growth Processes, MESH : Cell Hypoxia, MESH : Transfection, Subcellular Fractions, medicine.medical_specialty, MESH : Hypoxia-Inducible Factor 1, alpha Subunit, MESH: Cell Line, Tumor, Blotting, Western, Molecular Sequence Data, MESH : Deferoxamine, Down-Regulation, Breast Neoplasms, Cell Growth Processes, MESH : Subcellular Fractions, Deferoxamine, Biology, Transfection, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, 03 medical and health sciences, Cell Line, Tumor, Internal medicine, MESH : Cell Cycle, CCAAT-Enhancer-Binding Protein-alpha, medicine, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH: Transfection, MESH : Humans, MESH : Transcription, Genetic, MESH: Immunohistochemistry, MESH: Deferoxamine, Hypoxia-Inducible Factor 1, alpha Subunit, MESH : Promoter Regions (Genetics), Molecular biology, Endocrinology, HIF1A, MESH : Cell Growth Processes, MESH: Subcellular Fractions, MESH: Electrophoretic Mobility Shift Assay, biology.protein, MESH : Base Sequence, MESH: Breast Neoplasms
Abstract: International audience; The transcription factor CCAAT/enhancer binding protein-alpha (C/EBP alpha) is involved in the control of cell differentiation and proliferation, and has been suggested to act as a tumor suppressor in several cancers. By using microarray analysis, we have previously shown that hypoxia and estrogen down-regulate C/EBP alpha mRNA in T-47D breast cancer cells. Here, we have examined the mechanism by which the down-regulation by hypoxia takes place. Using the specific RNA polymerase II inhibitor 5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside, the mRNA stability was analyzed under normoxia or hypoxia by quantitative reverse transcription-PCR. Hypoxia reduced the half-life of C/EBP alpha mRNA by approximately 30%. C/EBP alpha gene promoter studies indicated that hypoxia also repressed the transcription of the gene and identified a hypoxia-responsive element (-522; -527 bp), which binds to hypoxia-inducible factor (HIF)-1 alpha, as essential for down-regulation of C/EBP alpha transcription in hypoxia. Immunocytochemical analysis showed that C/EBP alpha was localized in the nucleus at 21% O(2), but was mostly cytoplasmic under 1% O(2). Knockdown of HIF-1 alpha by RNAi restored C/EBP alpha to normal levels under hypoxic conditions. Immunohistochemical studies of 10 tumor samples did not show any colocalization of C/EBP alpha and glucose transporter 1 (used as a marker for hypoxia). Taken together, these results show that hypoxia down-regulates C/EBP alpha expression in breast cancer cells by several mechanisms, including transcriptional and posttranscriptional effects. The down-regulation of C/EBP alpha in hypoxia is mediated by HIF-1.
Published: 2008
Full Text: View/download PDF

6. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

Author: Maria Mamani-Matsuda, Frédéric Gauthier, Claude-Agnès Reynaud, Corinne Cordier, Capucine Picard, Damiana Lecoeuche, Jean-Claude Weill, Sandra K. Weller, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ligue Nationale contre le Cancer, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, and Weller, Sandra
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH: Immunoglobulin Variable Region, Immunoglobulin D, MESH: Variation (Genetics), 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Variable Region, MESH: Antigens, CD, 0303 health sciences, biology, MESH : Variation (Genetics), MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Articles, MESH: Infant, MESH: Immunoglobulin M, somatic hypermutation, "somatic hypermutation", MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: B-Lymphocyte Subsets, MESH : Spleen, MESH: Immunoglobulin mu-Chains, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Immunologic Memory, MESH: Gene Rearrangement, MESH : Immunoglobulin M, Immunology, Somatic hypermutation, "splenic marginal zone", chemical and pharmacologic phenomena, MESH : Immunoglobulin D, Article, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, Antigen, MESH : Antigens, CD27, MESH: B-Lymphocytes, MESH : Antigens, CD, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, MESH: Transcription, Genetic, MESH : Humans, Ig repertoire, Germinal center, MESH : Transcription, Genetic, Gene rearrangement, MESH : Gene Rearrangement, splenic marginal zone, B-1 cell, MESH: T-Lymphocytes, MESH : Immunoglobulin mu-Chains, Immunoglobulin M, biology.protein, 030215 immunology, MESH : B-Lymphocyte Subsets, "Ig repertoire"
Abstract: International audience; T cell-dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell-independent responses. We used this dissociation to analyze the repertoire diversification of IgM(+)IgD(+)CD27(+) B cells (also known as "IgM memory" B cells), comparing these cells with switched B cells in children
Published: 2008
Full Text: View/download PDF

7. In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle

Author: Françoise Valensi, Antoine Gessain, Christophe Nicot, Hittu Matta, Renaud Mahieux, Preet M. Chaudhary, Vincent Lacoste, Jean Gabarre, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Molecular genetics and Immunology, University of Kansas Medical Center [Lawrence], Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Division of Hematology-Oncology and the Hillman Cancer Center, University of Pittsburgh Medical Center, This work was supported by a grant from l'Association de Recherche sur le Cancer (ARC) and from la Fondation de France to RM and grants from NIH (CA85177 and CA124621) to PMC. VL and CN were supported by a bourse Pasteur‐Weissman and la Ligue Nationale Contre le Cancer respectively. RM was supported by a bourse Roux, from the Institut Pasteur and by INSERM., We thank Dr D. Gonzalez‐Dunia, J.S. Seeler and C. Royer‐Leveau for their help. We are indebted to Drs P. Charneau, J. Golay, N. Rice, L. Boxer, P. Murphy and W.C. Greene for generous gifts of reagents essential to the realization of this study. We thank Pr O. Hermine for providing us with some PEL fresh samples, and Dr Timothy Stinear for his critical comments., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Kansas Medical Center [Kansas City, KS, USA], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), University of Kansas Medical Center, Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Subjects: non-Hodgkinlymphoma, Transcription, Genetic, Genes, myb, [SDV]Life Sciences [q-bio], viruses, CASP8 and FADD-Like Apoptosis Regulating Protein, Gene Expression, MESH : Sarcoma, Kaposi, MESH : Herpesvirus 8, Human, MESH: Virus Activation, Receptors, G-Protein-Coupled, Transduction (genetics), molecular studies, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin/virology, Transduction, Genetic, MESH: Viral Proteins/metabolism, Virus latency, MESH : Virus Latency, MYB, MESH : Cell Transformation, Viral, Viral G-Protein Coupled Receptor, MESH : Viral Proteins, MESH: Lymphoma, AIDS-Related/metabolism, Lymphoma, AIDS-Related, Regulation of gene expression, MESH : Trans-Activators, 0303 health sciences, Lymphoma, Non-Hodgkin, MESH: Virus Latency, NF-kappa B, Hematology, Transfection, MESH : Immediate-Early Proteins, MESH: Transduction, Genetic, MESH: Gene Expression Regulation, Viral, MESH: Sarcoma, Kaposi/metabolism, MESH: Herpesvirus 8, Human/physiology, Virus Latency, 3. Good health, Lytic cycle, MESH: Cell Transformation, Viral, MESH : NF-kappa B, MESH : Genes, myb, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, MESH : Virus Activation, MESH : Receptors, G-Protein-Coupled, Primary effusion lymphoma, MESH : Transfection, MESH: NF-kappa B/metabolism, Gene Expression Regulation, Viral, MESH: Cell Line, Tumor, MESH: Gene Expression, animal structures, MESH : Transduction, Genetic, MESH : Lymphoma, AIDS-Related, Biology, MESH : Gene Expression Regulation, Viral, Immediate-Early Proteins, Proto-Oncogene Proteins c-myb, Viral Proteins, 03 medical and health sciences, MESH: Receptors, G-Protein-Coupled/metabolism, MESH: Sarcoma, Kaposi/virology, MESH: Trans-Activators/metabolism, Cell Line, Tumor, medicine, nuclear factor-jB, Humans, MESH : Lymphoma, Non-Hodgkin, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism, Sarcoma, Kaposi, 030304 developmental biology, B cells, MESH: Humans, MESH : Cell Line, Tumor, herpes virus, MESH: Lymphoma, AIDS-Related/virology, MESH: Transcription, Genetic, MESH: Transfection, MESH: Immediate-Early Proteins/metabolism, MESH : Humans, MESH: Proto-Oncogene Proteins c-myb/analysis, MESH : Transcription, Genetic, Kaposi sarcoma, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Transformation, Viral, medicine.disease, MESH : Proto-Oncogene Proteins c-myb, MESH : Gene Expression, MESH: Genes, myb, Trans-Activators, Cancer research, MESH: Lymphoma, Non-Hodgkin/metabolism, Virus Activation
Abstract: International audience; Primary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency.
Published: 2007
Full Text: View/download PDF

8. HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32)

Author: Virginie Penard-Lacronique, Isabelle André-Schmutz, Xin-Ying Su, Roland Berger, Paola Ballerini, Claudie Lemercier, Véronique Della-Valle, Francine Mugneret, Serge Romana, Michel Lessard, Isabelle Radford-Weiss, Marina Lafage-Pochitaloff, Olivier Bernard, Génétique des hémopathies humaines ( EMI 210 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Developpement Normal et Pathologique du Système Immunitaire, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Cytogénétique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, CHU Strasbourg, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des hémopathies humaines (EMI 210), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Oncogene Proteins, Fusion, Transcription, Genetic, T-Lymphocytes, BCL11B, Chromosomal translocation, MESH : Promoter Regions, Genetic, MESH : Oncogene Proteins, Fusion, Biochemistry, Jurkat cells, Translocation, Genetic, Jurkat Cells, MESH : Chromosomes, Human, Pair 5, 0302 clinical medicine, MESH : Translocation, Genetic, Transcription (biology), MESH: Jurkat Cells, Leukemia-Lymphoma, Adult T-Cell, MESH: Leukemia-Lymphoma, Adult T-Cell, MESH : Homeodomain Proteins, Promoter Regions, Genetic, MESH : Jurkat Cells, Oncogene Proteins, 0303 health sciences, MESH : Chromosomes, Human, Pair 14, MESH : Oncogene Proteins, MESH : Tumor Suppressor Proteins, Cell Differentiation, Hematology, Transfection, MESH: Translocation, Genetic, DNA-Binding Proteins, medicine.anatomical_structure, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, MESH : DNA-Binding Proteins, MESH : Repressor Proteins, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH: Chromosomes, Human, Pair 5, T cell, Immunology, Biology, 03 medical and health sciences, MESH: Oncogene Proteins, MESH: Promoter Regions, Genetic, MESH: Homeodomain Proteins, medicine, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Chromosomes, Human, Pair 14, Homeodomain Proteins, MESH : T-Lymphocytes, MESH: Humans, Recombinase activity, Tumor Suppressor Proteins, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Cell Biology, T lymphocyte, Molecular biology, MESH : Leukemia-Lymphoma, Adult T-Cell, Repressor Proteins, MESH: T-Lymphocytes, MESH: Chromosomes, Human, Pair 14, MESH: DNA-Binding Proteins, MESH: Oncogene Proteins, Fusion
Abstract: International audience; The t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation.
Published: 2006
Full Text: View/download PDF

9. Expression colique de l’interféron-γ et de l’interleukine-10 au cours de la maladie de Crohn et de la rectocolite ulcéro-hémorragique

Author: A. Sassi, Lamia Kallel, M. Ben Ahmed, Samir Boubaker, Hechmi Louzir, Béchir Zouari, Azza Filali, Jalel Boubaker, Service de gastroentérologie A, Hôpital de La Rabta Tunis, Laboratoire de Transmission, Contrôle et Immunobiologie des Infections ( LR11IPT02 ), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Institut Pasteur de Tunis, Département de médecine préventive et de statistiques, Faculté de Médecine de Tunis, Hôpital La Rabta [Tunis], Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Réseau International des Instituts Pasteur (RIIP)
Subjects: MESH: Interleukin-10, MESH : RNA, Messenger, [SDV]Life Sciences [q-bio], MESH: Down-Regulation, MESH : Down-Regulation, MESH: Biopsy, 0302 clinical medicine, MESH : Child, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Child, Gamma interferon, Medicine, MESH : Female, MESH : Colonoscopy, 0303 health sciences, MESH: Middle Aged, MESH : Immunity, Mucosal, MESH : RNA, Ribosomal, MESH : Reverse Transcriptase Polymerase Chain Reaction, General Medicine, MESH : Adult, MESH : Colitis, Ulcerative, MESH: Case-Control Studies, MESH: Colonoscopy, MESH: Intestinal Mucosa, MESH : Severity of Illness Index, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, MESH : Case-Control Studies, MESH: Gene Expression, MESH: Interferon-gamma, MESH : Male, MESH: Colitis, Ulcerative, MESH : Crohn Disease, MESH : Intestinal Mucosa, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH: Severity of Illness Index, MESH : Adolescent, MESH : Interleukin-10, MESH : Middle Aged, MESH: Colon, MESH : Interferon-gamma, MESH: RNA, Messenger, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Crohn Disease, [ SDV ] Life Sciences [q-bio], Crohn disease, business.industry, MESH: Transcription, Genetic, MESH : Gene Expression Profiling, MESH : Humans, MESH : Transcription, Genetic, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Colon, Molecular biology, MESH: Male, MESH : Gene Expression, MESH: Immunity, Mucosal, MESH : Biopsy, MESH: RNA, Ribosomal, business, MESH: Female
Abstract: Resume Objectif Le but de ce travail etait d’explorer l’expression colique de l’INF-γ et de l’IL-10 chez des patients atteints de maladie de Crohn (MC) ou de rectocolite ulcero-hemorragique (RCH). Methodes Quatorze patients atteints de MC et 11 atteints de RCH ont ete inclus, ainsi que 7 sujets temoins. L’etude de l’expression colique de l’INF-γ et de l’IL-10 a ete realisee sur des biopsies de colon sain et malade, en utilisant la technique de transcription inverse et d’amplification genique (RT-PCR) en temps reel (Taqman). Les resultats ont ete exprimes sous forme de rapport entre la quantite d’ARN messager (ARNm) de la cytokine et celle d’une molecule de reference, l’ARN ribosomal 18S, puis multiplie par 10 8 . Resultats En cas de maladie de Crohn, le colon exprimait plus d’INF-γ et d’IL-10 par rapport aux temoins (medianes respectives : 23,03 vs 1,87, p = 0,042 et 20,61 vs 2,13, p = 0,08). Une puissante correlation positive a ete trouvee entre l’expression colique de l’IL-10 et celle de l’INF-γ au cours de la MC (r = 0,9, p Au niveau des sites lesionnels de RCH, l’expression de l’INF-γ ainsi que celle de l’IL-10 etaient comparables a celles observees chez les temoins (7,18 vs 2,18, p = 0,36 et 3,66 vs 1,87, p = 0,44). Conclusion Au cours de la maladie de Crohn, l’expression de l’IL-10 et celle de l’INF-γ etaient plus elevees que chez les temoins et etroitement correlees.
Published: 2005
Full Text: View/download PDF

10. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR

Author: Marc Monot, Johann Peltier, Martine Pestel-Caron, Jean-Louis Pons, Olga Soutourina, Imane El Meouche, Bruno Dupuy, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Ecosystème intestinal, probiotiques, antibiotiques (EA 4065), Université Paris Descartes - Paris 5 (UPD5), Funding was provided by the University of Rouen., Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes ( GRAM 1.0 ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Pathogénèse des Bactéries Anaérobies, Institut Pasteur [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Ecosystème intestinal, probiotiques, antibiotiques ( EA 4065 ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: MESH : Protein Biosynthesis, Transcription, Genetic, Mutant, lcsh:Medicine, MESH : Transcriptome, MESH : Promoter Regions, Genetic, MESH: Base Sequence, Transcription (biology), Sigma factor, Gene expression, MESH : Bacterial Proteins, MESH: Gene Silencing, lcsh:Science, Promoter Regions, Genetic, MESH : Clostridium difficile, MESH: Bacterial Proteins, MESH : Consensus Sequence, Regulation of gene expression, Genetics, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, MESH: Genetic Complementation Test, Multidisciplinary, MESH : Protein Binding, DNA-Directed RNA Polymerases, MESH : Phenotype, Phenotype, Flagella, MESH: Protein Biosynthesis, MESH: Transcription Initiation Site, Transcription Initiation Site, MESH : Mutation, Research Article, Protein Binding, MESH : Gene Expression Regulation, Bacterial, MESH: Mutation, Bacterial Toxins, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, MESH: Phenotype, MESH: Flagella, 03 medical and health sciences, Bacterial Proteins, MESH : DNA-Directed RNA Polymerases, Consensus Sequence, MESH : Gene Silencing, MESH: Promoter Regions, Genetic, Consensus sequence, Position-Specific Scoring Matrices, MESH: Protein Binding, Gene Silencing, MESH: Consensus Sequence, Gene, MESH: Clostridium difficile, 030304 developmental biology, Binding Sites, Base Sequence, MESH : Genetic Complementation Test, Clostridioides difficile, 030306 microbiology, MESH: Transcription, Genetic, MESH: Transcriptome, lcsh:R, Genetic Complementation Test, MESH : Transcription, Genetic, MESH: Position-Specific Scoring Matrices, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, MESH : Position-Specific Scoring Matrices, MESH: DNA-Directed RNA Polymerases, Regulon, MESH: Bacterial Toxins, MESH: Binding Sites, MESH : Transcription Initiation Site, Protein Biosynthesis, Mutation, MESH : Bacterial Toxins, lcsh:Q, MESH : Base Sequence, Transcriptome, MESH : Flagella, MESH : Binding Sites
Abstract: International audience; Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA) and B (TcdB), whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.
Published: 2013
Full Text: View/download PDF

11. Targeting c-FLIP in cancer

Author: Olivier Micheau, Sarah Shirley, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, INCa (Polynom174), ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006), European Project, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), ANR-06-JCJC-0103, ANR--07-PCV-0031,ANR-06-JCJC-0103, ANR--07-PCV-0031, Micheau, Olivier, Programme 'Jeunes chercheuses et jeunes chercheurs' - TRAIL et chimiothérapies anticancéreuses - - TRAILCHIM2006 - ANR-06-JCJC-0103 - JCJC - VALID, Apoptrain, Marie Curie RTN - INCOMING, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: Cancer Research, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Transcription, Genetic, Regulator, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, MESH : Fas Ligand Protein, MESH : RNA, Small Interfering, Ligands, MESH : TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand, 0302 clinical medicine, Neoplasms, MESH: RNA, Small Interfering, MESH: Ligands, MESH: Neoplasms, RNA, Small Interfering, Death Receptors, Cancer, Regulation of gene expression, 0303 health sciences, MESH : Ligands, MESH: Gene Expression Regulation, Neoplastic, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, MESH : Antineoplastic Agents, Oncology, 030220 oncology & carcinogenesis, Death-inducing signaling complex, MESH: TNF-Related Apoptosis-Inducing Ligand, Programmed cell death, Fas Ligand Protein, c-FLIP, MESH : Gene Expression Regulation, Neoplastic, Antineoplastic Agents, Biology, 03 medical and health sciences, Downregulation and upregulation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Protein Processing, Post-Translational, MESH: Humans, MESH: Apoptosis, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH : Neoplasms, MESH: Fas Ligand Protein, Flip, MESH: Protein Processing, Post-Translational, Cancer cell, MESH: Antineoplastic Agents, Protein Processing, Post-Translational, MESH : Apoptosis
Abstract: International audience; Cellular-FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1. Three splice variants of c-FLIP function at the DISC level by blocking the processing and activation of procaspase-8 and -10. Overexpression of c-FLIP has been identified in many different tumour types, and its downregulation in vitro has been shown to restore apoptosis mediated by CD95L and TRAIL. c-FLIP therefore represents a promising target for cancer therapy. This review focuses on the molecular mechanisms that control c-FLIP expression and current research into inhibitors of the protein. Increasing evidence supports the investigation of c-FLIP as a therapeutic target to restore an apoptotic response in cancer cells.
Published: 2013
Full Text: View/download PDF

12. FISH-quant: automatic counting of transcripts in 3D FISH images

Author: Xavier Darzacq, Adrien Senecal, Edouard Bertrand, Nathalie Ly, Christophe Zimmer, Florian Mueller, Olivier Collin, Eugenia Basyuk, Hervé Marie-Nelly, Katjana Tantale, Imagerie et Modélisation, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This research was supported by the Agence Nationale de la Recherche (ANR-10-BLAN-1222, ANR-09-PIRI-0024, ANR-10-INTB-1401), Sidaction, the Région Ile-de-France under C'Nano IdF (the Center of Competences in NanoSciences for the Paris region), the Fondation pour la Recherche Médicale en France (FRM) and the Institut Pasteur, We thank J. McNally for editing the manuscript., ANR-09-PIRI-0024,Chromodyn(2009), ANR-10-BLAN-1222,IMAGenEx,Imagerie de l'expression génétique dans la cellule(2010), ANR-10-INTB-1401,RNAtrans,Visualisation de molécules uniques d'ARNm et de leur topologie afin d'étudier la traduction locale dans les neurones(2010), Mueller, Florian, Programme interdisciplinaire sur les systèmes biologiques et d'innovation biomédicale - - Chromodyn2009 - ANR-09-PIRI-0024 - PIRI - VALID, BLANC - Imagerie de l'expression génétique dans la cellule - - IMAGenEx2010 - ANR-10-BLAN-1222 - BLANC - VALID, Programme Blanc International édition 2010 - Visualisation de molécules uniques d'ARNm et de leur topologie afin d'étudier la traduction locale dans les neurones - - RNAtrans2010 - ANR-10-INTB-1401 - Blanc international 2010 - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie de l'ENS Paris (UMR 8197/1024) ( IBENS ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), ANR-09-PIRI-0024,Chromodyn,Mapping and modelling of chromosome dynamics ( 2009 ), ANR-10-BLAN-1222,IMAGenEx,Imagerie de l'expression génétique dans la cellule ( 2010 ), ANR-10-INTB-1401,RNAtrans,Visualisation de molécules uniques d'ARNm et de leur topologie afin d'étudier la traduction locale dans les neurones ( 2010 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS)
Subjects: MESH : RNA, Messenger, Transcription, Genetic, [SDV]Life Sciences [q-bio], MESH : Protein Subunits, MESH : Actins, MESH : Models, Biological, Biochemistry, 0302 clinical medicine, Image Processing, Computer-Assisted, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, Genetics, 0303 health sciences, medicine.diagnostic_test, Fluorescence in situ hybridization, MESH: Protein Subunits, MESH: Image Processing, Computer-Assisted, MESH : In Situ Hybridization, Fluorescence, [SDV] Life Sciences [q-bio], MESH: Reproducibility of Results, MESH : Computer Simulation, MESH : Imaging, Three-Dimensional, MESH : RNA Polymerase II, RNA Polymerase II, MESH : Image Processing, Computer-Assisted, Biotechnology, Computational biology, MESH: Imaging, Three-Dimensional, Biology, MESH: Actins, Models, Biological, 03 medical and health sciences, Imaging, Three-Dimensional, MESH: Computer Simulation, medicine, Computer Simulation, RNA, Messenger, Molecular Biology, Gene, 030304 developmental biology, MESH: RNA, Messenger, Messenger RNA, [ SDV ] Life Sciences [q-bio], MESH : Reproducibility of Results, MESH: Transcription, Genetic, MESH: Models, Biological, RNA, MESH : Transcription, Genetic, Reproducibility of Results, Cell Biology, Actins, Computational biology and bioinformatics, MESH: RNA Polymerase II, Protein Subunits, 030217 neurology & neurosurgery
Abstract: International audience; Transcription is inherently stochastic even in clonal cell populations 1. Studies at single-cell-single-molecule level enable a quantitative understanding of the underlying regulatory mechanisms 2,3. A widely used technique is single-molecule RNA fluorescence in-situ hybridization (FISH), in which fluorescent probes target the mRNA of interest and individual molecules appear as bright diffraction-limited spots (Fig. 1a,b) 3. Recent experimental progress makes FISH easy to use 4 , but a dedicated image analysis tool is currently missing. Available methods allow counting of isolated mature mRNAs but cannot reliably quantify the dense mRNA aggregates at transcription sites (TS) in three dimensions (3D), particularly of highly transcribing genes 4. We developed FISH-QUANT to close this gap (Supplementary Note 1)
Published: 2013
Full Text: View/download PDF

13. Annotation of microsporidian genomes using transcriptional signals

Author: Ivan Wawrzyniak, Sébastien Terrat, Olivier Gonçalves, Nicolas Parisot, Pierre Peyret, Patrick Wincker, Corinne Biderre-Petit, Simone Duprat, Frédéric Delbac, Jean Weissenbach, Sébastien Rimour, Eric Dugat-Bony, Antoine Mahul, Gaelle Samson, Brigitte Chebance, Stéphanie Bornes, Jérémie Denonfoux, Eric Peyretaillade, Michael Katinka, Valérie Polonais, Conception, Ingénierie et Développement de l'Aliment et du Médicament ( CIDAM ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes ( LIMOS ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Sigma CLERMONT ( Sigma CLERMONT ) -Centre National de la Recherche Scientifique ( CNRS ), Génie Biologie, Genoscope - Centre national de séquençage [Evry] ( GENOSCOPE ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Génomique métabolique ( UMR 8030 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Conception, Ingénierie et Développement de l'Aliment et du Médicament (CIDAM), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Genomic platform and R&D, GenoScreen, Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Ressources Informatiques (CRRI), Clermont Université, Bioprocédés Appliqués aux Microalgues (GEPEA-BAM), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), IUT Génie Biologique, Laboratoire de Biologie, Université d'Auvergne (Clermont Ferrand 1) (UdA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Structure et évolution des génomes (SEG), CNS-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Mines de St Etienne, Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: Transcription, Genetic, genome annotation, MESH : Molecular Sequence Annotation, General Physics and Astronomy, MESH: Phosphotransferases, Genome, transcriptional signal, MESH : Protein Transport, MESH : Fungal Proteins, DNA, Fungal, Conserved Sequence, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Fungal protein, MESH: Conserved Sequence, Multidisciplinary, MESH: Genomics, 030302 biochemistry & molecular biology, Genomics, Genome project, Protein Transport, Molecular Sequence Annotation, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Genome, Fungal, MESH: Fungal Proteins, MESH : Phosphotransferases, Genome, Fungal, Transposable element, MESH: Protein Transport, Genes, Fungal, MESH: Molecular Sequence Annotation, MESH : Microsporidia, MESH : Open Reading Frames, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Fungal Proteins, Open Reading Frames, 03 medical and health sciences, MESH : Conserved Sequence, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Anncaliia algerae, parasitic diseases, Gene, 030304 developmental biology, bioinformatic, MESH: Transcription, Genetic, MESH : Genome, Fungal, Phosphotransferases, structural annotation, MESH : Genomics, fungi, MESH : Transcription, Genetic, General Chemistry, MESH: Open Reading Frames, MESH: Microsporidia, MESH: DNA, Fungal, microsporidia, MESH : Genes, Fungal, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH : DNA, Fungal, MESH: Genes, Fungal
Abstract: EA GenoSol CT3; International audience; High-quality annotation of microsporidian genomes is essential for understanding the biological processes that govern the development of these parasites. Here we present an improved structural annotation method using transcriptional DNA signals. We apply this method to re-annotate four previously annotated genomes, which allow us to detect annotation errors and identify a significant number of unpredicted genes. We then annotate the newly sequenced genome of Anncaliia algerae. A comparative genomic analysis of A. algerae permits the identification of not only microsporidian core genes, but also potentially highly expressed genes encoding membrane-associated proteins, which represent good candidates involved in the spore architecture, the invasion process and the microsporidian-host relationships. Furthermore, we find that the ten-fold variation in microsporidian genome sizes is not due to gene number, size or complexity, but instead stems from the presence of transposable elements. Such elements, along with kinase regulatory pathways and specific transporters, appear to be key factors in microsporidian adaptive processes.
Published: 2012
Full Text: View/download PDF

14. Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes

Author: Alain Minn, Daniela Gradinaru, Jean-Marie Heydel, Anne-Laure Minn, Yves Artur, University of Medicine and Pharmacy, Carol Davila University, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Conseil Regional de Bourgogne, Dijon, France, EU-COST Action on Chemistry of Non-Enzymatic Protein Modifications [CM1001], Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Pharmacologie, and Université de Vandœuvre-lès-Nancy
Subjects: MESH : Oxidative Stress, MESH : RNA, Messenger, Antioxidant, Transcription, Genetic, medicine.medical_treatment, Toxicology, NAD(P)H:quinone oxidoreductase 1, MESH: Glucuronosyltransferase, Antioxidants, Substrate Specificity, Rats, Sprague-Dawley, 0302 clinical medicine, MESH: NADPH-Ferrihemoprotein Reductase, MESH: Glucuronides, NAD(P)H Dehydrogenase (Quinone), MESH : Catalysis, MESH: Animals, MESH : NAD(P)H Dehydrogenase (Quinone), Glucuronosyltransferase, Cells, Cultured, chemistry.chemical_classification, MESH : Cell Survival, 0303 health sciences, MESH : Substrate Specificity, MESH : Animals, Newborn, Cytochrome P450 reductase, General Medicine, MESH: Cell Survival, MESH: Pyridinium Compounds, MESH : Antioxidants, MESH: Cells, Cultured, Oxidative phosphorylation, Gene Expression Regulation, Enzymologic, MESH : Quinones, MESH : Glucuronides, 03 medical and health sciences, RNA, Messenger, Cell Shape, NADPH-Ferrihemoprotein Reductase, MESH : Oxidation-Reduction, MESH : Pyridinium Compounds, MESH: Naphthols, MESH : Glucuronosyltransferase, MESH: Antioxidants, MESH: Catalysis, chemistry, Oxidative stress, Astrocytes, Reactive Oxygen Species, 030217 neurology & neurosurgery, MESH: Oxidation-Reduction, Time Factors, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Reactive Oxygen Species, NADPH:cytochrome P450 reductase, Pyridinium Compounds, Naphthols, MESH: Rats, Sprague-Dawley, Protein oxidation, medicine.disease_cause, MESH: Animals, Newborn, MESH: NAD(P)H Dehydrogenase (Quinone), Protein Carbonylation, MESH : Oxidants, MESH: Oxidants, Melatonin, MESH: Melatonin, MESH: Oxidative Stress, MESH : Melatonin, MESH : Rats, MESH: Gene Expression Regulation, Enzymologic, Quinones, MESH: Reactive Oxygen Species, Oxidants, Biochemistry, MESH : Protein Carbonylation, Oxidation-Reduction, UDP-glucuronosyltransferase, MESH : Time Factors, MESH: Protein Carbonylation, MESH: Rats, Cell Survival, MESH : Naphthols, Biology, Catalysis, MESH: Quinones, MESH : Gene Expression Regulation, Enzymologic, Glucuronides, MESH : Cells, Cultured, medicine, Animals, MESH: Cell Shape, 030304 developmental biology, MESH: RNA, Messenger, Reactive oxygen species, MESH: Transcription, Genetic, MESH: Time Factors, MESH : Astrocytes, MESH : Transcription, Genetic, MESH : Rats, Sprague-Dawley, Rats, MESH: Astrocytes, Animals, Newborn, MESH : NADPH-Ferrihemoprotein Reductase, MESH: Substrate Specificity, MESH : Animals, NAD+ kinase, MESH : Cell Shape, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: WOS:000309170300003; International audience; The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression.
Published: 2012
Full Text: View/download PDF

15. Physiological relevance and contribution to metal balance of specific and non-specific Metallothionein isoforms in the garden snail, Cantareus aspersus

Author: Reinhard Dallinger, Sílvia Pérez-Rafael, Annette de Vaufleury, Martina Höckner, Karin Stefanon, Òscar Palacios, Sílvia Atrian, Freddy Monteiro, Mercè Capdevila, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut für Zoologie, Universität Innsbruck [Innsbruck], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: MESH : Molecular Sequence Data, Transcription, Genetic, [ SDV.TOX.ECO ] Life Sciences [q-bio]/Toxicology/Ecotoxicology, MESH: Amino Acid Sequence, MESH: Protein Isoforms, 010501 environmental sciences, 01 natural sciences, Mass Spectrometry, MESH: Recombinant Proteins, Transcription (biology), MESH: Helix (Snails), Metallothionein, Protein Isoforms, MESH: Animals, MESH : Copper, Peptide sequence, Chromatography, High Pressure Liquid, MESH : Cadmium, 0303 health sciences, Cadmium, biology, Ecology, MESH : Amino Acid Sequence, MESH : Sequence Alignment, Metals and Alloys, Recombinant Proteins, MESH: Copper, Biochemistry, MESH : Helix (Snails), [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, General Agricultural and Biological Sciences, Gene isoform, MESH : Recombinant Proteins, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Cadmium, chemistry.chemical_element, Sequence alignment, Pulmonata, General Biochemistry, Genetics and Molecular Biology, Biomaterials, 03 medical and health sciences, MESH : Chromatography, High Pressure Liquid, MESH : Mass Spectrometry, Animals, Amino Acid Sequence, MESH: Chromatography, High Pressure Liquid, Gene, 030304 developmental biology, 0105 earth and related environmental sciences, MESH: Mass Spectrometry, MESH: Molecular Sequence Data, MESH: Transcription, Genetic, Helix, Snails, MESH: Metallothionein, MESH : Transcription, Genetic, MESH : Protein Isoforms, biology.organism_classification, MESH : Metallothionein, chemistry, MESH : Animals, Sequence Alignment, Copper
Abstract: International audience; Variable environmental availability of metal ions represents a constant challenge for most organisms, so that during evolution, they have optimised physiological and molecular mechanisms to cope with this particular requirement. Metallothioneins (MTs) are proteins that play a major role in metal homeostasis and as a reservoir. The MT gene/protein systems of terrestrial helicid snails are an invaluable model for the study of metal-binding features and MT isoform-specific functionality of these proteins. In the present study, we characterised three paralogous MT isogenes and their expressed products in the escargot (Cantareus aspersus). The metal-dependent transcriptional activation of the three isogenes was assessed using quantitative Real Time PCR. The metal-binding capacities of the three isoforms were studied by characterising the purified native complexes. All the data were analysed in relation to the trace element status of the animals after metal feeding. Two of the three C. aspersus MT (CaMT) isoforms appeared to be metal-specific, (CaCdMT and CaCuMT, for cadmium and copper respectively). A third isoform (CaCd/CuMT) was non-specific, since it was natively recovered as a mixed Cd/Cu complex. A specific role in Cd detoxification for CaCdMT was revealed, with a 80-90% contribution to the Cd balance in snails exposed to this metal. Conclusive data were also obtained for the CaCuMT isoform, which is involved in Cu homeostasis, sharing about 30-50% of the Cu balance of C. aspersus. No apparent metal-related physiological function was found for the third isoform (CaCd/CuMT), so its contribution to the metal balance of the escargot may be, if at all, of only marginal significance, but may enclose a major interest in evolutionary studies.
Published: 2011
Full Text: View/download PDF

16. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection

Author: David Durantel, Olivier Hantz, Silke Arzberger, Ulrike Protzer, Fabien Zoulim, Laura Belloni, Massimo Levrero, Michel Strubin, Julie Lucifora, Physiopathologie moléculaire et nouveaux traitements des hépatites virales, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Technische Universität München [München] ( TUM ), Equipee 16, Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Rome la Sapienza, Departement of internal medicine and laboratory of gene expression, equipe 15, Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Molecular Infectiology - Center for Molecular Medicine Cologne, Institute for Medical Microbiology, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL)
Subjects: HBV RNA encapsidation signal epsilon, Transcription, Genetic, viruses, MESH : Hepatitis B virus, MESH : Hepatocytes, medicine.disease_cause, Virus Replication, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hepatocytes, MESH : Hepatitis B e Antigens, 0302 clinical medicine, Hepatitis B Surface Antigens/metabolism, hbx protein, heparg, hepatitis b virus, natural infection, primary human hepatocytes, Viral Regulatory and Accessory Proteins, Hepatitis B e Antigens, MESH : DNA, Viral, MESH: Hepatitis B e Antigens, DNA, Circular/metabolism, ddc:616, 0303 health sciences, MESH : Trans-Activators, DNA, Viral/metabolism, MESH : Hep G2 Cells, virus diseases, cccDNA, Hep G2 Cells, Hepatitis B, 3. Good health, MESH : Virus Replication, HBx, MESH: Hepatitis B virus, MESH : DNA, Circular, MESH: DNA, Circular, 030211 gastroenterology & hepatology, DNA, Circular, MESH : Transfection, Hepatitis B X-Protein, Hepatitis B virus, MESH: Trans-Activators, MESH: Hep G2 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Transfection, Hepatitis B virus PRE beta, 03 medical and health sciences, Hepatitis B virus/genetics/physiology, Antigen, medicine, Humans, Trans-Activators/genetics/physiology, 030304 developmental biology, Hepatitis B Surface Antigens, MESH: Humans, MESH : Hepatitis B Surface Antigens, Hepatology, MESH: Hepatitis B, MESH: Transcription, Genetic, MESH: Transfection, MESH: Virus Replication, MESH : Humans, MESH : Transcription, Genetic, MESH : Hepatitis B, Virology, Molecular biology, digestive system diseases, MESH: DNA, Viral, MESH: Hepatitis B Surface Antigens, Hepatitis B/virology, Viral replication, Hepatitis B e Antigens/metabolism, DNA, Viral, Trans-Activators, Hepatocytes
Abstract: International audience; BACKGROUND & AIMS: The molecular biology of hepatitis B virus (HBV) has been extensively studied but the exact role of the hepatitis B X protein (HBx) in the context of natural HBV infections remains unknown. METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing conditional trans complementation of HBx were infected with wild type (HBV(wt)) or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication was followed. RESULTS: We observed that cells inoculated with HBx-deficient HBV particles (HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and nuclear import, active transcription was only observed from HBV(wt) genomes. Trans-complementation of HBx was able to rescue transcription from the HBV(x-) genome and led to antigen and virion secretion, even weeks after infection. Constant expression of HBx was necessary to maintain HBV antigen expression and replication. Finally, we demonstrated that HBx is not packaged into virions during assembly but is expressed after infection within the new host cell to allow epigenetic control of HBV transcription from cccDNA. CONCLUSIONS: Our results demonstrate that HBx is required to initiate and maintain HBV replication and highlight HBx as the key regulator during the natural infection process.
Published: 2011
Full Text: View/download PDF

17. The Sm-like RNA chaperone Hfq mediates transcription antitermination at Rho-dependent terminators

Author: Rabhi, Makhlouf, Espéli, Olivier, Schwartz, Annie, Cayrol, Bastien, Rahmouni, a Rachid, Arluison, Véronique, Boudvillain, Marc, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire Bioénergétique Membranaire et Stress (LBMS), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bioénergétique, Métalloprotéines et Stress ( LBMS ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Escherichia coli, MESH : Molecular Sequence Data, Transcription, Genetic, MESH : Transcription Factors, MESH: Peptide Elongation Factors, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, MESH: Terminator Regions, Genetic, MESH: Escherichia coli Proteins, MESH: Host Factor 1 Protein, Host Factor 1 Protein, MESH: Base Sequence, Article, Escherichia coli, MESH: Adenosine Triphosphatases, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Peptide Elongation Factors, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adenosine Triphosphatases, Terminator Regions, Genetic, MESH: Gene Expression Regulation, Bacterial, MESH: Molecular Sequence Data, Base Sequence, MESH : Adenosine Triphosphatases, MESH : Terminator Regions, Genetic, MESH: RNA Helicases, MESH: Escherichia coli, Escherichia coli Proteins, MESH : Escherichia coli Proteins, MESH: Transcription, Genetic, MESH : Host Factor 1 Protein, MESH : Molecular Chaperones, MESH : Transcription, Genetic, Gene Expression Regulation, Bacterial, MESH: Transcription Factors, MESH : RNA, Bacterial, Peptide Elongation Factors, MESH : RNA Helicases, RNA, Bacterial, MESH : Electrophoretic Mobility Shift Assay, MESH: Electrophoretic Mobility Shift Assay, MESH : Base Sequence, MESH: Molecular Chaperones, MESH: RNA, Bacterial, RNA Helicases, Molecular Chaperones, Transcription Factors, MESH : Gene Expression Regulation, Bacterial
Abstract: International audience; In Escherichia coli, the essential motor protein Rho promotes transcription termination in a tightly controlled manner that is not fully understood. Here, we show that the general post-transcriptional regulatory protein Hfq associates with Rho to regulate Rho function. The Hfq:Rho complex can be further stabilized by RNA bridging both factors in a configuration that inhibits the ATP hydrolysis and duplex unwinding activities of Rho and that mediates transcription antitermination at Rho-dependent terminators in vitro and in vivo. Antitermination at a prototypical terminator (λtR1) requires Hfq binding to an A/U-rich transcript region directly upstream from the terminator. Antitermination is modulated by trans-acting factors (NusG or nucleic acid competitors) that affect Hfq association with Rho or RNA. These data unveil a new Hfq function and a novel transcription regulatory mechanism with potentially important implications for bacterial RNA metabolism, gene silencing, and pathogenicity.
Published: 2011
Full Text: View/download PDF

18. Effects of a high-fat diet on energy metabolism and ROS production in rat liver

Author: Anne Galinier, Hervé Dubouchaud, Nellie Taleux, Karine Couturier, Cécile Cottet-Rousselle, Louis Casteilla, Anne Athias, Xavier Leverve, Guillaume Vial, Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Métabolisme, plasticité et mitochondrie, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Hamant, Sarah
Subjects: Mitochondrial ROS, Male, Transcription, Genetic, MESH : Reactive Oxygen Species, Mitochondria, Liver, MESH : Hepatocytes, Mitochondrion, Oxidative Phosphorylation, MESH: Hepatocytes, 0302 clinical medicine, MESH: Membrane Potential, Mitochondrial, Citrate synthase, MESH: Animals, Beta oxidation, MESH : Electron Transport, 2. Zero hunger, Membrane Potential, Mitochondrial, 0303 health sciences, MESH : Rats, Adenine nucleotide translocator, MESH: Energy Metabolism, MESH: Reactive Oxygen Species, Lipids, Biochemistry, Liver, MESH: Dietary Fats, Mitochondrial matrix, 030220 oncology & carcinogenesis, Body Composition, MESH : Oxidative Phosphorylation, ATP–ADP translocase, MESH: Mitochondria, Liver, MESH: Rats, MESH : Body Composition, MESH : Male, Oxidative phosphorylation, Biology, MESH : Rats, Wistar, Electron Transport, 03 medical and health sciences, MESH: Oxidative Phosphorylation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, MESH: Electron Transport, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Hepatology, MESH: Transcription, Genetic, MESH : Transcription, Genetic, MESH : Liver, MESH : Lipids, MESH: Body Composition, MESH: Rats, Wistar, MESH: Lipids, Dietary Fats, MESH: Male, Rats, MESH : Energy Metabolism, MESH : Membrane Potential, Mitochondrial, MESH : Mitochondria, Liver, biology.protein, Hepatocytes, MESH : Animals, Energy Metabolism, Reactive Oxygen Species, MESH : Dietary Fats, MESH: Liver
Abstract: International audience; BACKGROUND & AIMS: A high-fat diet affects liver metabolism, leading to steatosis, a complex disorder related to insulin resistance and mitochondrial alterations. Steatosis is still poorly understood since diverse effects have been reported, depending on the different experimental models used. METHODS: We hereby report the effects of an 8 week high-fat diet on liver energy metabolism in a rat model, investigated in both isolated mitochondria and hepatocytes. RESULTS: Liver mass was unchanged but lipid content and composition were markedly affected. State-3 mitochondrial oxidative phosphorylation was inhibited, contrasting with unaffected cytochrome content. Oxidative phosphorylation stoichiometry was unaffected, as were ATPase and adenine nucleotide translocator proteins and mRNAs. Mitochondrial acylcarnitine-related H(2)O(2) production was substantially higher and the mitochondrial quinone pool was smaller and more reduced. Cellular consequences of these mitochondrial alterations were investigated in perifused, freshly isolated hepatocytes. Ketogenesis and fatty acid-dependent respiration were lower, indicating a lower β-oxidation rate contrasting with higher RNA contents of CD36, FABP, CPT-1, and AcylCoA dehydrogenases. Concomitantly, the cellular redox state was more reduced in the mitochondrial matrix but more oxidized in the cytosol: these opposing changes are in agreement with a significantly higher in situ mitochondrial proton motive force. CONCLUSIONS: A high-fat diet results in both a decrease in mitochondrial quinone pool and a profound modification in mitochondrial lipid composition. These changes appear to play a key role in the resulting inhibition of fatty acid oxidation and of mitochondrial oxidative-phosphorylation associated with an increased mitochondrial ROS production. Mitochondrial quinone pool could have prospects as a crucial event, potentially leading to interesting therapeutic perspectives.
Published: 2011
Full Text: View/download PDF

19. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Author: Anderson Miyoshi, Vasco Azevedo, Lisa Ott, Andreas Burkovski, Flávia S. Rocha, Fernanda Alves Dorella, Olivier Join-Lambert, Eva Trost, Samer Kayal, Alexander Goesmann, Nicole Guiso, Peter Husemann, Jens Stoye, Artur Silva, Andreas Tauch, Vivian D'Afonseca, Sebastian Jaenicke, Jerónimo Saiz Ruiz, Siomar de Castro Soares, Jessica Schneider, Jasmin Schröder, Institut für Genomforschung und Systembiologie, Universität Bielefeld-Centrum für Biotechnologie, CLIB Graduate Cluster Industrial Biotechnology, Lehrstuhl für Mikrobiologie, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Bioinformatics Resource Facility, AG Genominformatik, Universität Bielefeld-Technische Fakultät, Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas [Goiânia, Brésil] (ICB)-Universidade Federal de Minas Gerais, Cellular and Molecular Parasitology / Parasitologia Celular e Molecular [Belo Horizonte, Brésil], Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto de Ciências Biológicas, Federal University of Para - Universidade Federal do Pará - UFPA [Belém, Brazil] (UFPA), Prévention et Thérapie Moléculaires des Maladies Infectieuses Humaines, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Médecine-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Bielefeld University and the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia. LO and AB were supported by the Deutsche Forschungsgemeinschaft in frame of SFB 796 (project B5)., BMC, Ed., Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Federal University of Para - Universidade Federal do Para [Belem - Brésil], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centrum für Biotechnologie-Universität Bielefeld, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Instituto de Ciências Biológicas [Goiânia, Brésil] ( ICB ) -Universidade Federal de Minas Gerais, Cellular and Molecular Parasitology Laboratory, Rene Rachou Research Center-Fundação Oswaldo Cruz ( FIOCRUZ ), Universidade Federal do Pará, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Faculté de Médecine-CHU Necker - Enfants Malades [AP-HP]
Subjects: MESH : Virulence Factors, MESH: Sequence Analysis, DNA, Transcription, Genetic, Corynebacterium pseudotuberculosis, MESH : Molecular Sequence Annotation, MESH: Base Sequence, MESH: Virulence, MESH: Genome, Bacterial, MESH: Zinc, MESH : Iron, Bacterial Adhesion, MESH : Child, MESH: Child, MESH : Female, Gene Regulatory Networks, Child, Pathogen, Histiocytic Necrotizing Lymphadenitis, MESH: Gene Regulatory Networks, 0303 health sciences, MESH: Iron, Virulence, MESH : Genes, Bacterial, MESH : Fimbriae, Bacterial, MESH : Virulence, Zinc, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Regulon, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, DNA microarray, MESH: Genes, Bacterial, Research Article, Biotechnology, lcsh:QH426-470, MESH : Bacterial Adhesion, Virulence Factors, Iron, lcsh:Biotechnology, MESH : Genome, Bacterial, MESH : Regulon, MESH: Manganese, MESH: Molecular Sequence Annotation, Biology, Regulon, Microbiology, MESH: Fimbriae, Bacterial, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, Genetics, Humans, MESH: Bacterial Adhesion, 030304 developmental biology, MESH: Virulence Factors, Whole genome sequencing, Manganese, MESH : Corynebacterium pseudotuberculosis, MESH: Humans, Base Sequence, 030306 microbiology, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Molecular Sequence Annotation, MESH : Zinc, MESH : Histiocytic Necrotizing Lymphadenitis, Sequence Analysis, DNA, MESH: Corynebacterium pseudotuberculosis, MESH: Histiocytic Necrotizing Lymphadenitis, lcsh:Genetics, Genes, Bacterial, MESH : Gene Regulatory Networks, Fimbriae, Bacterial, Pyrosequencing, Caseous lymphadenitis, MESH : Base Sequence, MESH : Manganese, MESH: Female, Genome, Bacterial, MESH : Sequence Analysis, DNA
Abstract: Background Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated. Results Sequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence. Conclusion The functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.
Published: 2010
Full Text: View/download PDF

20. The consequences of regulation of desat1 expression for pheromone emission and detection in Drosophila melanogaster

Author: François Bousquet, Benjamin Houot, Jean-François Ferveur, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: Fatty Acid Desaturases, Male, Transcription, Genetic, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Animals, Genetically Modified, MESH : Genotype, MESH: Genotype, Animals, Genetically Modified, Sexual Behavior, Animal, MESH : Hydrocarbons, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Drosophila melanogaster, Drosophila Proteins, MESH: Animals, MESH : Female, MESH: Sexual Behavior, Animal, Sex Attractants, Genetics, MESH: Nursing Assessment, MESH : Craniocerebral Trauma, biology, MESH : Gene Expression Regulation, Reverse Transcriptase Polymerase Chain Reaction, MESH : Fatty Acid Desaturases, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Fatty Acid Desaturases, MESH: Gene Expression Regulation, Phenotype, MESH: Intracranial Pressure, MESH: Sex Attractants, Drosophila melanogaster, Sex pheromone, Pheromone, Female, MESH : Mutation, MESH: Mutation, Genotype, MESH : Coma, MESH: Drosophila Proteins, MESH : Male, MESH: Craniocerebral Trauma, Sensory system, Locus (genetics), Investigations, MESH: Drosophila melanogaster, MESH: Animals, Genetically Modified, MESH: Hydrocarbons, MESH: Education, Nursing, Continuing, MESH : Nursing Assessment, Animals, MESH : Sexual Behavior, Animal, Gene, MESH: Coma, Transcriptional activity, MESH : Sex Attractants, MESH: Humans, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, biology.organism_classification, MESH : Drosophila Proteins, MESH: Male, Hydrocarbons, MESH : Intracranial Pressure, Gene Expression Regulation, Mutation, MESH : Animals, MESH : Education, Nursing, Continuing, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Sensory communication depends on the precise matching between the emission and the perception of sex- and species-specific signals; understanding both the coevolutionary process and the genes involved in both production and detection is a major challenge. desat1 determines both aspects of communication—a mutation in desat1 simultaneously alters both sex pheromone emission and perception in Drosophila melanogaster flies. We investigated whether the alteration of pheromonal perception is a consequence of the altered production of pheromones or if the two phenotypes are independently controlled by the same locus. Using several genetic tools, we were able to separately manipulate the two pheromonal phenotypes, implying that desat1 is the sole gene responsible, exerting a pleiotropic effect on both transmission and detection. The levels of the five desat1 trancripts, measured in the head and body of manipulated flies, were related to variation in pheromone production. This suggests that the pleiotropic action of desat1 on pheromonal communication depends on the fine regulation of its transcriptional activity.
Published: 2010
Full Text: View/download PDF

21. In vivo and in vitro tools to identify and study transcriptional regulation of USF-1 target genes

Author: Marie-Dominique Galibert, Sébastien Corre, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and De Villemeur, Hervé
Subjects: Pro-Opiomelanocortin, Time Factors, Transcription, Genetic, p38 Mitogen-Activated Protein Kinases, 0302 clinical medicine, Transcription (biology), MESH: Reverse Transcriptase Polymerase Chain Reaction, Gene expression, Transcriptional regulation, MESH: Pro-Opiomelanocortin, Luciferases, MESH : Pro-Opiomelanocortin, MESH : p38 Mitogen-Activated Protein Kinases, 0303 health sciences, Pigmentation, Reverse Transcriptase Polymerase Chain Reaction, Receptors, Melanocortin, MESH : Pigmentation, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Upstream Stimulatory Factors, Cell biology, 030220 oncology & carcinogenesis, MESH : Time Factors, MESH: Enzyme Activation, MESH: Cell Line, Tumor, Ultraviolet Rays, Biology, MESH: Pigmentation, 03 medical and health sciences, In vivo, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Luciferase, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, Transcription factor, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Receptors, Melanocortin, MESH : Luciferases, MESH: Humans, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH : Humans, MESH: Time Factors, MESH : Receptors, Melanocortin, MESH : Transcription, Genetic, MESH : Upstream Stimulatory Factors, In vitro, Enzyme Activation, MESH: p38 Mitogen-Activated Protein Kinases, MESH : Ultraviolet Rays, Upstream Stimulatory Factors, MESH: Ultraviolet Rays, MESH: Luciferases, MESH : Enzyme Activation
Abstract: In: Transcription Factors: Methods and Protocols. Higgins, Paul J. (Ed.) 1st Edition., 2010, 377 p. 172 illus., 86 in color., ISBN: 978-1-60761-737-2; International audience; In response to environmental stress, cells trigger a number of molecular mechanisms to control their survival and growth. These include changes in gene expression with corresponding Post-translational modifications to critical transcriptional-control proteins. Transcription is a highly-regulated process that is impacted by a large number of ubiquitous and specific factors. In order to determine how gene expression is regulated in response to environmental cues, it is necessary to correlate modifications to specific transcription proteins with an accurate assessment of the transcriptional response. This chapter details quantitative Real Time PCR (qPCR) and Luciferase assay protocols to illustrate, both in vivo and in vitro, the role of the USF-1 transcription factor in the UV-dependant regulation of pigmentation genes (POMC and MC1R). The procedures have been optimized for the USF-1 transcription factor and the regulation of specific target genes in response to physiological UV doses.
Published: 2010
Full Text: View/download PDF

22. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

Author: Ovidiu Radulescu, Bernard Delyon, Olivier Delattre, Tatiana Baumuratova, Anne Siegel, Didier Surdez, Gautier Stoll, Service de Biologie Systémique [Luxembourg], Université du Luxembourg (Uni.lu)-Faculté des Sciences, de la Technologie et de la Communication (FSTC), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), ANR-06-BYOS-0004,SITCON,Modeling signal transduction induced by a chimeric oncogene(2006), Université du Luxembourg ( Uni.lu ) -Faculté des Sciences, de la Technologie et de la Communication (FSTC), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Dynamique des interactions membranaires normales et pathologiques ( DIMNP ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Biological systems and models, bioinformatics and sequences ( SYMBIOSE ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ), ANR-06-BYOS-0004,SITCON,Modeling signal transduction induced by a chimeric oncogene ( 2006 ), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, BMC, Ed., Biologie systémique (BIOSYS) - Modeling signal transduction induced by a chimeric oncogene - - SITCON2006 - ANR-06-BYOS-0004 - BIOSYS - VALID, and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 )
Subjects: Transcription, Genetic, MESH: Oncogenes, MESH: Insulin-Like Growth Factor I, Gene regulatory network, MESH : Insulin-Like Growth Factor I, Sarcoma ewing, MESH: Insulin-Like Growth Factor Binding Proteins, Multidisciplinaire, généralités & autres [F99] [Sciences du vivant], 0302 clinical medicine, Structural Biology, Gene Regulatory Networks, Insulin-Like Growth Factor I, MESH : Insulin-Like Growth Factor Binding Protein 3, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Insulin-Like Growth Factor Binding Proteins/genetics, MESH: Gene Regulatory Networks, Genetics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Proto-Oncogene Protein c-fli-1, Methodology Article, Applied Mathematics, MESH : Insulin-Like Growth Factor Binding Proteins, MESH: Insulin-Like Growth Factor Binding Protein 3, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH: Sarcoma, Ewing, Insulin-Like Growth Factor Binding Proteins, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Modeling and Simulation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Software, [ INFO.INFO-IR ] Computer Science [cs]/Information Retrieval [cs.IR], MESH: Cell Line, Tumor, Systems biology, Sarcoma, Ewing, Computational biology, Multidisciplinary, general & others [F99] [Life sciences], Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Software, Qualitative analysis, Modelling and Simulation, Cell Line, Tumor, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Molecular Biology, 030304 developmental biology, MESH : Oncogenes, Oncogenes/genetics, Sarcoma, Ewing/genetics, MESH: Humans, Proto-Oncogene Protein c-fli-1, MESH : Cell Line, Tumor, Specific-information, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Transcription, Genetic, MESH : Humans, Experimental data, Ewing's sarcoma, MESH : Transcription, Genetic, Oncogenes, medicine.disease, MESH : Proto-Oncogene Protein c-fli-1, Gene expression profiling, Insulin-Like Growth Factor Binding Protein 3, MESH : Sarcoma, Ewing, lcsh:Biology (General), Proto-Oncogene Protein c-fli-1/genetics, MESH : Gene Regulatory Networks, [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], [INFO.INFO-IR] Computer Science [cs]/Information Retrieval [cs.IR], Insulin-Like Growth Factor I/genetics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Software
Abstract: Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.
Published: 2010
Full Text: View/download PDF

23. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome

Author: André Baruchel, Yves Perel, Anne Hagemejier, Guy Leverger, Judith Landman-Parker, Paola Ballerini, Virginie Gandemer, François Sigaux, Gérard Michel, Claudine Schmitt, Vahid Asnafi, Jean Michel Cayuela, Sylvie Fasola, Marie Françoise Auclerc, Luc Douay, Thierry Leblanc, Myriam Labopin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'hématologie, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'onco-hématologie pédiatrique, hôpital Sud, Service d'hématologie pédiatrique et oncologie, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie, Service d'oncologie et hématologie, Hôpital d'enfants, Department of Human Genetics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), supported by Chugai France (Dr. Thierry Guillot) and SFCE (Société Française des Cancers de l'Enfant)., Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Sud, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Catholic University of Leuven ( KU Leuven ), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), and De Villemeur, Hervé
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Oncology, Time Factors, Transcription, Genetic, MESH : Genotype, MESH : Child, Preschool, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, 0302 clinical medicine, MESH : Child, hemic and lymphatic diseases, MESH: Child, Gene expression, Genotype, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia-Lymphoma, Adult T-Cell, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Medicine, MESH : Female, MESH : Homeodomain Proteins, MESH: Leukemia-Lymphoma, Adult T-Cell, Child, Regulation of gene expression, 0303 health sciences, MESH : Prognosis, Hematology, Hazard ratio, MESH : Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Follow-Up Studies, MESH: Gene Expression Regulation, Neoplastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Adult, Prognosis, MESH : Survival Rate, MESH: Infant, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, NUP214-ABL1, Child, Preschool, 030220 oncology & carcinogenesis, outcome, Female, France, TLX3/HOX11L2, MESH : Time Factors, Adult, medicine.medical_specialty, Adolescent, MESH: Survival Rate, MESH : Gene Expression Regulation, Neoplastic, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Adolescent, Internal medicine, MESH: Homeodomain Proteins, Humans, MESH : France, Survival rate, 030304 developmental biology, Homeodomain Proteins, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, MESH: Transcription, Genetic, MESH : Humans, MESH: Time Factors, MESH: Child, Preschool, Infant, MESH : Transcription, Genetic, childhood T-cell acute lymphoblastic leukemia, MESH : Follow-Up Studies, MESH: Adult, MESH : Leukemia-Lymphoma, Adult T-Cell, MESH: Male, MESH: France, El Niño, Fusion transcript, Immunology, SIL-TAL1, business, MESH: Female, Follow-Up Studies
Abstract: International audience; BACKGROUND: The prognostic value of the ectopic activation of TLX3 gene expression, a major oncogenetic event associated with pediatric T-cell acute lymphoblastic leukemia, is controversial. Likewise, the frequency and the prognostic significance in pediatric T-cell acute lymphoblastic leukemia of the newly characterized NUP214-ABL1 fusion transcript is not yet clear. DESIGN AND METHODS: Two hundred children with T-cell acute lymphoblastic leukemia were treated in the French FRALLE-93 study from 1993 to 1999. The expression of TLX3, TLX1 and SILTAL1 genes was analyzed in samples from 92 patients by real-time quantitative reverse transcriptase polymerase chain reaction. Most of these samples were further studied for NUP214-ABL1 and CALM-AF10 fusion transcripts. RESULTS: The median follow-up was 7.9 years. At 5 years the overall survival (+/- standard deviation, %) was 62 (+/-3%) and leukemia-free survival was 58 (+/-3%). Patients with T-cell acute lymphoblastic leukemia positive for TLX3 had a poorer survival compared to those with T-ALL negative for TLX3 (overall survival: 45+/-11% vs. 57+/-5%, p=0.049). In multivariate analysis, TLX3 expression was an independent adverse risk factor predicting relapse with a hazard ratio of 2.44 (p=0.017) and an overall survival with a hazard ratio of 3.7 (p=0.001). NUP214-ABL1 was expressed in 16.6% of patients with TLX3-positive T-ALL (3 of 18); all of the patients with this association died before completion of the treatment. SILTAL expression did not significantly affect the prognosis of patients with T-cell acute lymphoblastic leukemia. Only three of 92 patients expressed the TLX1 gene and all three are alive. CONCLUSIONS: TLX3 gene expression is an independent risk factor predicting poor survival in childhood T-cell acute lymphoblastic leukemia. When co-expressed with TLX3, NUP214-ABL1 transcripts may increase the risk of poor survival.
Published: 2008
Full Text: View/download PDF

24. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women

Author: Claus Holst, Nathalie Vega, Moira A. Taylor, J. Alfredo Martínez, Eva Klimcakova, Thorkild I. A. Sørensen, Dominique Langin, Sébastien Déjean, Jean M. Oppert, Peter Arner, Hubert Vidal, Nathalie Viguerie, Karine Clément, Frédéric Capel, Wim H. M. Saris, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Midicine Karolinska Institute, Karolinska University Hospital Huddinge, Department of Sports Medicine of Charles University, Faculty of Medicine Charles University, Department of Physiology and nutrition University of Navarra, Universidad de Navarra [Pamplona] (UNAV), Department of Human Biology Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], The Netherlands Institute of Preventive Medicine, Institute of Preventive Medicine, School of Biomedical Sciences Queen's Medical Center, University of Nottingham Medical School, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Nutrition and Endocrinology AP / HP, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Navarra [Pamplona] ( UNAV ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, Endocrinology, Diabetes and Metabolism, MESH: Energy Intake, Biochemistry, Body Mass Index, 0302 clinical medicine, Endocrinology, Gene expression, MESH: Genetic Variation, MESH : Adaptor Proteins, Signal Transducing, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Addipose tissue, Reducing, MESH: Mitochondrial Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, Body Composition, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, MESH : Adipose Tissue, MESH: Body Mass Index, MESH : Receptors, Glucocorticoid, 03 medical and health sciences, MESH: Weight Loss, Genetic, Humans, MESH : Fatty Acid-Binding Proteins, MESH : Mitochondrial Proteins, MESH: Adaptor Proteins, Signal Transducing, MESH: Humans, MESH : Humans, Signal Transducing, Genetic Variation, MESH: Adult, Autophagy-Related Protein 8 Family, MESH: Body Composition, medicine.disease, Obesity, MESH : Energy Metabolism, MESH : Body Mass Index, Energy intake, Body mass index, MESH: Female, Candidate gene, MESH: Receptors, Glucocorticoid, Clinical Biochemistry, Adipose tissue, Blood lipids, Glucocorticoid, Weight loss, Sirtuin 3, Receptors, MESH : RNA, Sirtuins, MESH: Obesity, MESH : Female, Nutrición y dietética [Ciencias de la Salud], MESH : Diet, Reducing, 2. Zero hunger, MESH : Sirtuins, MESH: Diet, Reducing, Microfilament Proteins, MESH: Energy Metabolism, Adaptor Proteins, MESH : Adult, MESH: Sirtuins, MESH : Obesity, Female, medicine.symptom, Transcription, Adult, MESH : Microfilament Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Mitochondrial Proteins, MESH: Microfilament Proteins, Receptors, Glucocorticoid, MESH : Genetic Variation, MESH: RNA, Internal medicine, Weight Loss, medicine, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MESH: Transcription, Genetic, Biochemistry (medical), MESH : Transcription, Genetic, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, RNA, MESH : Weight Loss, Energy Intake, Energy Metabolism
Abstract: Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and, the fat and carbohydrate content of the diet. Design & setting: Obese subjects recruited among 8 European clinical centers followed 10 weeks of either a low fat (high carbohydrate) or a moderate fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. A thousand genes were regulated by energy restriction. We validated an effect of the fat-to-carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA and GABARAPL2) with increased expression during the moderate fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. AD - INSERM, U858, Laboratoire de Recherches sur les Obesites, Institut de Medecine Moleculaire de Rangueil, Toulouse; Universite Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse; Centre Hospitalier Universitaire de Toulouse, France; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; INSERM, UMR -870; INRA U-1235; Faculte de Medecine Lyon-Sud universite de Lyon 1; Centre de Recherche en Nutrition Humaine, Hospices civils de Lyon; Lyon, France; Institut de Mathematiques de Toulouse UMR 5219, Universite Paul-Sabatier, Toulouse, France; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain; Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Institute of Preventive Medicine, Centre for Health and Society, Copenhagen University Hospital, Copenhagen, Denmark; School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham Medical School, Nottingham, United Kingdom; INSERM, Nutriomique U872 (Team 7), 75004 Paris, France; Universites Pierre et Marie Curie-Paris6, UMR-S 872, Cordelier Research Center & Paris Descartes, 75006 Paris; and Assistance Publique/Hopitaux de Paris (AP-HP), Pitie Salpetriere Hospital, Nutrition and Endocrinology department, 75013 Paris, France.
Published: 2008
Full Text: View/download PDF

25. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver

Author: Léon Kautz, Annabelle Monnier, Delphine Meynard, Marie-Paule Roth, Régis Bouvet, Valérie Darnaud, Chiuxia Deng, Hélène Coppin, Jean Mosser, Sophie Vaulont, Rui-Hong Wang, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Moléculaire et Génomique, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR, programme IRONGENES, Commission européenne (LSHM-CT-2006-037296 : EUROIRON1), Association pour la Recherche sur le Cancer (ARC), ANR-05-MRAR-0031,IRONGENES,Intégration d'approches génétiques et génomiques pour l'identification des gènes modificateurs impliqués dans l'hémochromatose génétique(2005), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), ANR: IRONGENES,IRONGENES, Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecosystèmes, biodiversité, évolution [Rennes] ( ECOBIO ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -INEE-Observatoire des Sciences de l'Univers de Rennes ( OSUR ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), ANR : IRONGENES,IRONGENES, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique moléculaire et Génomique [CHU Rennes], and CHU Pontchaillou [Rennes]
Subjects: Male, MESH: Signal Transduction, Transcription, Genetic, MESH : Basic Helix-Loop-Helix Transcription Factors, Bone Morphogenetic Protein 6, MESH: Bone Morphogenetic Protein 6, MESH: Bone Morphogenetic Proteins, Smad Proteins, SMAD, Biochemistry, MESH: Mice, Knockout, MESH : Iron, Mice, MESH : Phosphorylation, MESH : Smad1 Protein, MESH : Bone Morphogenetic Proteins, 0302 clinical medicine, Transcription (biology), Gene expression, MESH: Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, MESH: Smad4 Protein, MESH: Animals, Phosphorylation, Smad4 Protein, Mice, Knockout, 2. Zero hunger, 0303 health sciences, MESH: Iron, biology, MESH : Smad5 Protein, Hematology, Erythroferrone, Cell biology, Liver, 030220 oncology & carcinogenesis, Bone Morphogenetic Proteins, MESH: Smad7 Protein, Signal transduction, MESH : Smad7 Protein, Signal Transduction, Smad5 Protein, Iron Overload, Iron, MESH : Male, Immunology, Active Transport, Cell Nucleus, MESH: Active Transport, Cell Nucleus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Smad1 Protein, Smad7 Protein, MESH : Diet, 03 medical and health sciences, MESH: Smad5 Protein, MESH: Gene Expression Profiling, MESH: Iron Overload, MESH: Diet, Hepcidin, MESH : Mice, Animals, MESH : Smad Proteins, MESH: Mice, MESH : Active Transport, Cell Nucleus, 030304 developmental biology, Hemojuvelin, MESH : Signal Transduction, MESH : Iron Overload, MESH: Phosphorylation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Transcription, Genetic, MESH: Smad1 Protein, MESH : Transcription, Genetic, MESH : Liver, MESH : Smad4 Protein, MESH: Smad Proteins, Cell Biology, MESH: Male, Diet, Smad8 Protein, biology.protein, MESH : Mice, Knockout, MESH: Smad8 Protein, MESH : Animals, MESH : Smad8 Protein, MESH : Bone Morphogenetic Protein 6, MESH: Liver
Abstract: Although hepcidin expression was shown to be induced by the BMP/Smad signaling pathway, it is not yet known how iron regulates this pathway and what its exact molecular targets are. We therefore assessed genome-wide liver transcription profiles of mice of 2 genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts significantly modulated by the dietary iron content, 4 were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 all related to the Bmp/Smad pathway. As shown by Western blot analysis, variations in Bmp6 expression induced by the diet iron content have for functional consequence similar changes in Smad1/5/8 phosphorylation that leads to formation of heteromeric complexes with Smad4 and their translocation to the nucleus. Gene expression variations induced by secondary iron deficiency or iron overload were compared with those consecutive to Smad4 and Hamp1 deficiency. Iron overload developed by Smad4- and Hamp1-deficient mice also increased Bmp6 transcription. However, as shown by analysis of mice with liver-specific disruption of Smad4, activation of Smad7, Id1, and Atoh8 transcription by iron requires Smad4. This study points out molecules that appear to play a critical role in the control of systemic iron balance.
Published: 2008
Full Text: View/download PDF

26. Two RNA polymerase I subunits control the binding and release of Rrn3 during transcription

Author: Beckouet, Frédéric, Labarre-Mariotte, Sylvie, Albert, Benjamin, Imazawa, Yukiko, Werner, Michel, Gadal, Olivier, Nogi, Yasuhisa, Kwapisz, Marta, BECKOUET, Frederic, Thuriaux, Pierre, Service de Biologie Intégrative et Génétique Moléculaire (SBIGeM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Biologie Intégrative et Génétique Moléculaire ( SBIGeM ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de biologie moléculaire eucaryote du CNRS ( LBME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, MESH : Molecular Sequence Data, MESH : Transcription Factors, Transcription, Genetic, MESH: RNA Polymerase I, MESH: Sequence Homology, Amino Acid, [SDV]Life Sciences [q-bio], MESH : Protein Subunits, MESH : Saccharomyces cerevisiae, RNA polymerase II, MESH: Amino Acid Sequence, chemistry.chemical_compound, MESH : Mycophenolic Acid, 0302 clinical medicine, MESH: Saccharomyces cerevisiae Proteins, Sigma factor, RNA Polymerase I, RNA polymerase, Enzyme Inhibitors, ComputingMilieux_MISCELLANEOUS, Polymerase, MESH: Chromatin Immunoprecipitation, 0303 health sciences, biology, MESH : RNA Polymerase I, MESH : Amino Acid Sequence, MESH : Protein Binding, Articles, MESH: Transcription Factors, MESH : Schizosaccharomyces pombe Proteins, MESH: Protein Subunits, MESH: Saccharomyces cerevisiae, MESH : Sequence Homology, Amino Acid, MESH: Schizosaccharomyces, MESH : Dimerization, MESH: Enzyme Inhibitors, Transcription factor II D, MESH : Mutation, Dimerization, Pol1 Transcription Initiation Complex Proteins, MESH: Models, Molecular, Plasmids, Protein Binding, MESH : Pol1 Transcription Initiation Complex Proteins, Chromatin Immunoprecipitation, Saccharomyces cerevisiae Proteins, MESH: Mutation, MESH : Models, Molecular, Termination factor, Molecular Sequence Data, RNA-dependent RNA polymerase, Saccharomyces cerevisiae, MESH: Two-Hybrid System Techniques, MESH : Saccharomyces cerevisiae Proteins, 03 medical and health sciences, MESH : Chromatin Immunoprecipitation, MESH: Plasmids, Two-Hybrid System Techniques, Schizosaccharomyces, RNA polymerase I, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH: Pol1 Transcription Initiation Complex Proteins, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Mycophenolic Acid, MESH : Enzyme Inhibitors, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, MESH: Transcription, Genetic, MESH : Transcription, Genetic, MESH: Schizosaccharomyces pombe Proteins, Cell Biology, Mycophenolic Acid, Molecular biology, Protein Subunits, chemistry, MESH : Schizosaccharomyces, MESH : Two-Hybrid System Techniques, MESH: Dimerization, MESH : Plasmids, Mutation, biology.protein, Schizosaccharomyces pombe Proteins, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; Rpa34 and Rpa49 are nonessential subunits of RNA polymerase I, conserved in species from Saccharomyces cerevisiae and Schizosaccharomyces pombe to humans. Rpa34 bound an N-terminal region of Rpa49 in a two-hybrid assay and was lost from RNA polymerase in an rpa49 mutant lacking this Rpa34-binding domain, whereas rpa34Delta weakened the binding of Rpa49 to RNA polymerase. rpa34Delta mutants were caffeine sensitive, and the rpa34Delta mutation was lethal in a top1Delta mutant and in rpa14Delta, rpa135(L656P), and rpa135(D395N) RNA polymerase mutants. These defects were shared by rpa49Delta mutants, were suppressed by the overexpression of Rpa49, and thus, were presumably mediated by Rpa49 itself. rpa49 mutants lacking the Rpa34-binding domain behaved essentially like rpa34Delta mutants, but strains carrying rpa49Delta and rpa49-338::HIS3 (encoding a form of Rpa49 lacking the conserved C terminus) had reduced polymerase occupancy at 30 degrees C, failed to grow at 25 degrees C, and were sensitive to 6-azauracil and mycophenolate. Mycophenolate almost fully dissociated the mutant polymerase from its ribosomal DNA (rDNA) template. The rpa49Delta and rpa49-338::HIS3 mutations had a dual effect on the transcription initiation factor Rrn3 (TIF-IA). They partially impaired its recruitment to the rDNA promoter, an effect that was bypassed by an N-terminal deletion of the Rpa43 subunit encoded by rpa43-35,326, and they strongly reduced the release of the Rrn3 initiation factor during elongation. These data suggest a dual role of the Rpa49-Rpa34 dimer during the recruitment of Rrn3 and its subsequent dissociation from the elongating polymerase.
Published: 2008
Full Text: View/download PDF

27. Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect

Author: Diane Rebourcet, Sangeeta Y. Devi, Nadine Binart, Carlos Stocco, Nancy D. Leslie, Geula Gibori, Julia Halperin, Aurora Shehu, Jamie Le, Terry G. Unterman, Shai E. Elizur, Department of Physiology and Biophysics, College of Medicine of Chicago, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Medecine, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Cincinnati Children's Hospital Medical Center, Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and University of Illinois at Chicago ( UIC )
Subjects: MESH: Signal Transduction, endocrine system diseases, Transcription, Genetic, MESH : Genotype, Electrophoretic Mobility Shift Assay, MESH : Blotting, Western, MESH: Mice, Knockout, MESH: Genotype, Mice, Endocrinology, Ovarian Follicle, MESH : Prolactin, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Female, MESH: Animals, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Receptor, Mice, Knockout, Regulation of gene expression, MESH : Gene Expression Regulation, Reverse Transcriptase Polymerase Chain Reaction, Forkhead Box Protein O3, MESH : Reverse Transcriptase Polymerase Chain Reaction, Forkhead Transcription Factors, General Medicine, MESH: Gene Expression Regulation, MESH : Mice, Transgenic, Premature ovarian failure, Cell biology, MESH : Forkhead Transcription Factors, medicine.anatomical_structure, MESH : Electrophoretic Mobility Shift Assay, FOXO3, Female, Signal transduction, Signal Transduction, MESH: Ovary, medicine.medical_specialty, endocrine system, MESH: Cell Line, Tumor, Genotype, Receptors, Prolactin, MESH: Mice, Transgenic, MESH : Ovarian Follicle, Blotting, Western, MESH: Prolactin, Mice, Transgenic, Ovary, Biology, Article, MESH: Receptors, Prolactin, MESH: Forkhead Transcription Factors, Cell Line, Tumor, Internal medicine, MESH : Mice, medicine, Animals, Humans, UTP-Hexose-1-Phosphate Uridylyltransferase, MESH: Blotting, Western, Ovarian follicle, Molecular Biology, Transcription factor, MESH: Mice, MESH : Receptors, Prolactin, MESH : Ovary, MESH : Signal Transduction, MESH: Humans, MESH: UTP-Hexose-1-Phosphate Uridylyltransferase, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, MESH : UTP-Hexose-1-Phosphate Uridylyltransferase, medicine.disease, MESH: Ovarian Follicle, Prolactin, Gene Expression Regulation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Electrophoretic Mobility Shift Assay, MESH : Mice, Knockout, MESH : Animals, MESH: Female
Abstract: Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation.
Published: 2008
Full Text: View/download PDF

28. Agr system of Listeria monocytogenes EGD-e: role in adherence and differential expression pattern

Author: Dominique Garmyn, Jean Guzzo, Stéphanie Weidmann, Pascal Piveteau, Aurélie Rieu, Laboratoire de Recherche en Vigne et Vin (REVV), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB), Microbiologie du Sol et de l'Environnement (MSE), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Laboratoire de Recherche en Vigne et Vin ( REVV ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Microbiologie du Sol et de l'Environnement ( MSE ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: MESH : RNA, Messenger, Transcription, Genetic, Operon, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, MESH: Listeria monocytogenes, Applied Microbiology and Biotechnology, Bacterial Adhesion, Rapid amplification of cDNA ends, Transcription (biology), MESH : Bacterial Proteins, MESH : DNA, Bacterial, MESH: Bacterial Proteins, 0303 health sciences, MESH : Trans-Activators, MESH: Gene Expression Regulation, Bacterial, Ecology, cell-to-cell communication, MESH : Biofilms, Biotechnology, MESH : Gene Expression Regulation, Bacterial, DNA, Bacterial, MESH : Bacterial Adhesion, MESH: Trans-Activators, Genetics and Molecular Biology, MESH: Biofilms, Biology, agr system, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Bacterial Proteins, medicine, MESH: Bacterial Adhesion, RNA, Messenger, Gene, 030304 developmental biology, MESH: RNA, Messenger, Messenger RNA, 030306 microbiology, MESH: Transcription, Genetic, Biofilm, MESH : Transcription, Genetic, Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Molecular biology, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biofilms, biofilm formation, Trans-Activators, MESH : Listeria monocytogenes, Bacteria, Food Science
Abstract: In this study, we investigated the agrBDCA operon in the pathogenic bacterium Listeria monocytogenes EGD-e. In-frame deletion of agrA and agrD resulted in an altered adherence and biofilm formation on abiotic surfaces, suggesting the involvement of the agr system of L. monocytogenes during the early stages of biofilm formation. Real-time PCR experiments indicated that the transcript levels of agrBDCA depended on the stage of biofilm development, since the levels were lower after the initial attachment period than during biofilm growth, whereas transcription during planktonic growth was not growth phase dependent. The mRNA quantification data also suggested that the agr system was autoregulated and pointed to a differential expression of the agr genes during sessile and planktonic growth. Although the reverse transcription-PCR experiments revealed that the four genes were transcribed as a single messenger, chemical half-life and 5′ RACE (rapid amplification of cDNA ends) experiments indicated that the full size transcript underwent cleavage followed by degradation of the agrC and agrA transcripts, which suggests a complex regulation of agr transcription.
Published: 2007
Full Text: View/download PDF

29. Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors

Author: Mandard, Stéphane, Stienstra, Rinke, Escher, Pascal, Tan, Nguan Soon, Kim, Insook, Gonzalez, Frank, Wahli, Walter, Desvergne, Béatrice, Müller, Michael, Kersten, Sander, Nutrition, Metabolism and Genomics group and Nutrigenomics Consortium ( NMG ), Wageningen University and Research Centre [Wageningen] ( WUR ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institute of Physiology, University of Basel ( Unibas ), Center for Integrative Genomics - Institute of Bioinformatics, Génopode ( CIG ), University of Lausanne, Laboratory of Metabolism, National Cancer Institute ( NIH ), This study was supported by the Netherlands Organization for Scientific Research (NWO), with additional support from the Dutch Diabetes Foundation, the Royal Netherlands Academy of Art and Sciences (KNAW), Wageningen Center for Food Sciences, the Center for Human Nutrigenomics, the Swiss National Science Foundation and the Human Frontier Science Program., Nutrition, Metabolism and Genomics group and Nutrigenomics Consortium (NMG), Wageningen University and Research [Wageningen] (WUR), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), University of Basel (Unibas), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), National Cancer Institute [Bethesda] (NCI-NIH), and National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)
Subjects: MESH: DNA Primers, MESH: Rats, glycogen synthase 2, MESH: Peroxisome Proliferator-Activated Receptors, MESH : Hepatocytes, PPRE, liver, MESH: Mice, Knockout, PPAR, MESH: Chromatin, MESH : Gene Expression Regulation, Enzymologic, MESH: Hepatocytes, MESH: RNA, MESH : Mice, MESH : RNA, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, HNF4α, MESH : Polymerase Chain Reaction, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Glycogen Synthase, MESH : Chromatin, MESH : Rats, MESH: Transcription, Genetic, MESH: Gene Expression Regulation, Enzymologic, MESH : Transcription, Genetic, MESH: Polymerase Chain Reaction, MESH : Peroxisome Proliferator-Activated Receptors, adipose tissue, gene transcription, MESH : Mice, Knockout, MESH : DNA Primers, MESH : Animals, microarray, MESH : Glycogen Synthase
Abstract: International audience; Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes. In liver, PPARalpha deletion leads to decreased glycogen levels in the refed state, which is paralleled by decreased expression of Gys-2 in fasted and refed state. Two putative PPAR response elements (PPREs) were identified in the mouse Gys-2 gene: one in the upstream promoter (DR-1prom) and one in intron 1 (DR-1int). It is shown that DR-1int is the response element for PPARs, while DR-1prom is the response element for Hepatic Nuclear Factor 4 alpha (HNF4alpha). In adipose tissue, which does not express HNF4alpha, DR-1prom is occupied by PPARbeta/delta and PPARgamma, yet binding does not translate into transcriptional activation of Gys-2. Overall, we conclude that mouse Gys-2 is a novel PPAR target gene and that transactivation by PPARs and HNF4alpha is mediated by two distinct response elements.
Published: 2007
Full Text: View/download PDF

30. Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells

Author: Yves Jacquot, Denis Nonclercq, Guy Laurent, Anny Cleeren, Alain Xicluna, Laurent Bermont, Kamal Boubekeur, Ioanna Laïos, Guy Leclercq, Bernard Refouvelet, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Histology, Faculty of Medicine and Pharmacy, Université de Mons-Hainaut, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Chimie Inorganique et Matériaux Moléculaires (CIM2), Laboratoire de catalyse de Lille - UMR 8010 (LCL), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Synthèse, Structure et Fonction de Molécules Bioactives ( SSFMB ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Mons-Hainaut (UMH), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire de Chimie Inorganique et Matériaux Moléculaires ( CIM2 ), Laboratoire de catalyse de Lille ( LCL ), and Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille ( ENSCL ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Models, Molecular, Transcription, Genetic, Clinical Biochemistry, Pharmaceutical Science, Estrogen receptor, MESH : Breast Neoplasms, MESH : Promoter Regions, Genetic, Ligands, 01 natural sciences, Biochemistry, MESH: Estrogens, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Transactivation, MESH : Tumor Cells, Cultured, Coumarins, Drug Discovery, Tumor Cells, Cultured, MESH : Cell Proliferation, MESH: Ligands, MESH : Transcriptional Activation, Luciferases, Promoter Regions, Genetic, MESH : Ligands, 0303 health sciences, Molecular Structure, Chemistry, Biological activity, Transfection, MESH: Coumarins, MESH : Thymidine Kinase, 3. Good health, Cell biology, MESH : Antineoplastic Agents, Receptors, Estrogen, Molecular Medicine, MESH: Receptors, Estrogen, MESH: Models, Molecular, medicine.drug, Transcriptional Activation, MESH: Thymidine Kinase, medicine.medical_specialty, MESH : Models, Molecular, MESH: Molecular Structure, Antineoplastic Agents, Breast Neoplasms, MESH : Coumarins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Thymidine Kinase, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, MESH: Promoter Regions, Genetic, medicine, Humans, MESH: Tumor Cells, Cultured, Molecular Biology, Cell Proliferation, 030304 developmental biology, MESH : Luciferases, MESH: Humans, Fulvestrant, 010405 organic chemistry, Cell growth, MESH: Transcription, Genetic, MESH : Humans, Organic Chemistry, MESH : Transcription, Genetic, Estrogens, Antiestrogen, 0104 chemical sciences, Endocrinology, Cell culture, MESH : Receptors, Estrogen, MESH: Antineoplastic Agents, MESH: Transcriptional Activation, MESH : Estrogens, MESH: Luciferases, MESH : Molecular Structure, MESH: Breast Neoplasms
Abstract: International audience; A number of coumarins exhibit interesting pharmacological activities and are therefore of therapeutic use. We report here the synthesis and the structural analysis of new N-substituted 4-amino-3-(2-methylbenzyl)coumarins (compounds 8a-8e) that present structural analogies with estrothiazine and 11- or 7-substituted 17beta-estradiol. These derivatives were tested with respect to estrogenic activity on the estrogen receptor positive (ER+) human MCF-7 breast cancer cell line. Two of the reported compounds (8a and 8b) stimulated specifically the proliferation of MCF-7 cells, but not that of estrogen receptor negative (ER-) human MDA-MB-231 breast cancer cells, suggesting that their mitogenic activity is mediated by ER. Accordingly, the stimulating effect of 8a and 8b was suppressed by the pure antiestrogen fulvestrant. Besides, 8a and 8b induced ER down-regulation similar to that produced by classical ER agonists or pure antagonists. The effects of the compounds under study on ER-mediated transcription were assessed on (ER+) MVLN cells, that is, MCF-7 cells stably transfected with a pVit-tk-Luc reporter plasmid. Derivatives 8a and 8b, and surprisingly compound 8c, enhanced ER-mediated gene transactivation in that model. Finally, no coumarin was able to compete with tritiated 17beta-estradiol ([(3)H]E(2)) for ER binding, suggesting unconventional interactions with the receptor, such as interactions with the second binding pocket or with the coactivator-binding region. To conclude, observations performed in this study on compound 8c reveal that estrogenic activity can be dissociated from enhancement of cell proliferation. Furthermore, ERE-driven transactivation of transcription seems to be a condition necessary, but not sufficient, for estrogen-induced stimulation of cell growth.
Published: 2007
Full Text: View/download PDF

31. Partial defects in transcriptional activity of two novel DAX-1 mutations in childhood-onset adrenal hypoplasia congenita

Author: Paul Laissue, Silvia Copelli, Marc Fellous, Gabriel Barrio, César Bergadá, Sinan Karaboga, Jean Marie Wurtz, Reiner A. Veitia, Ignacio Bergadá, Enzo Lalli, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departamento de Ciencias Biologicas, Universidad CAECE, Centro de Investigaciones Endocrinológicas (CEDIE), Hospital de Niños 'Ricardo Gutiérrez', Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (UNS), and Université Côte d'Azur (UCA) - Université Côte d'Azur (UCA) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Transcription, Genetic, MESH : Hela Cells, Receptors, Retinoic Acid, Endocrinology, Diabetes and Metabolism, MESH : Immunohistochemistry, DNA Mutational Analysis, Mutant, MESH : Child, Preschool, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Endocrinology, MESH: Structure-Activity Relationship, MESH : Child, MESH: Child, Adrenal Glands, MESH : Structure-Activity Relationship, MESH: Adrenal Glands, MESH: DNA Mutational Analysis, Child, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH : Infant, Transfection, Immunohistochemistry, Protein subcellular localization prediction, MESH: Infant, MESH : Receptors, Retinoic Acid, DNA-Binding Proteins, MESH: Repressor Proteins, Child, Preschool, MESH: Adrenal Insufficiency, MESH : DNA-Binding Proteins, MESH : Mutation, MESH : Repressor Proteins, MESH : Transfection, MESH : Protein Structure, Tertiary, medicine.medical_specialty, MESH: Mutation, MESH : Male, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, Biology, MESH : Adrenal Glands, Structure-Activity Relationship, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, X-linked adrenal hypoplasia congenita, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epigenetics, Gene, 030304 developmental biology, MESH: Receptors, Retinoic Acid, MESH: Humans, DAX-1 Orphan Nuclear Receptor, MESH: Transcription, Genetic, MESH: Transfection, MESH : Humans, MESH: Child, Preschool, Infant, MESH : Transcription, Genetic, MESH: Immunohistochemistry, MESH : Adrenal Insufficiency, medicine.disease, MESH: Male, Protein Structure, Tertiary, Repressor Proteins, MESH: Hela Cells, Nuclear receptor, Mutation, DAX1, MESH: DNA-Binding Proteins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Adrenal Insufficiency, HeLa Cells
Abstract: OBJECTIVE: Mutations in DAX-1, an X-linked gene encoding an orphan nuclear receptor, have been associated with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Here we describe two novel DAX-1 mutations, Y214X and I361T, associated with childhood-onset primary adrenal failure. We aimed at analysing their effects on protein localization, transcriptional activity and propose a structural-function relationship. DESIGN: We have directly sequenced the DAX-1 gene from PCR-amplified DNA. The effect of the mutations on protein localization was assessed by immunocytochemistry in transfected cells. The impact of mutations on transcriptional activity was determined by transfection using a StAR promoter-luciferase reporter system. RESULTS: The mutation Y214X produces a protein lacking the C-terminal half of DAX-1. The other one, I361T, affects a highly conserved amino acid within the putative ligand-binding domain. The mutant Y214X displayed a wild-type subcellular localization while I361T was partially retained in the cytoplasm. Both mutants retained subtantial transcriptional repressive activity, compared to mutants producing early onset adrenal failure. Interestingly, I361T displayed similar in vitro transcriptional repressive activity to the mutant I439S previously described in a case of late-onset AHC. This shows that molecular alterations of DAX-1 leading to similar in vitro activities may result in very different ages of onset of adrenal failure, which suggests that additional genetic and epigenetic factors are important in determining the clinical course of AHC. CONCLUSIONS: Our results help the understanding of structure-function relationships in the DAX-1 molecule, suggesting that the N-terminal domain is relatively autonomous and add credence to presumed molecular interactions within ligand binding domain of the protein.
Published: 2006
Full Text: View/download PDF

32. Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-alpha on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells

Author: Jean-Luc Prétet, J. F. Charlot, Christiane Mougin, Magali Nicolier, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Transcription, Genetic, MESH : Hela Cells, Cell, Mutant, Apoptosis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, HeLa, 0302 clinical medicine, MESH: Nerve Tissue Proteins, MESH : Cell Transformation, Viral, Enzyme Inhibitors, MESH: Tumor Suppressor Protein p53, 0303 health sciences, MESH : Cell Line, Transformed, DNA, Neoplasm, Pifithrin, Cell biology, Drug Combinations, MESH : Drug Combinations, MESH: Epithelial Cells, 030220 oncology & carcinogenesis, DNA fragmentation, MESH: Membrane Proteins, MESH : Cell Culture Techniques, MESH: Mitochondria, MESH: Toluene, 03 medical and health sciences, Humans, MESH: Membrane Potentials, MESH: Benzothiazoles, MESH: Drug Combinations, Pharmacology, MESH: Cell Culture Techniques, MESH: Humans, MESH : bcl-2-Associated X Protein, MESH : Humans, Epithelial Cells, Staurosporine, Thiazoles, chemistry, MESH : Membrane Proteins, Mutation, MESH: Female, MESH : Apoptosis, HeLa Cells, Cancer Research, MESH : Staurosporine, Clinical Biochemistry, Cell Culture Techniques, Pharmaceutical Science, MESH : Benzothiazoles, Membrane Potentials, chemistry.chemical_compound, MESH: Papillomaviridae, MESH : Thiazoles, MESH : Membrane Potentials, MESH : Female, Papillomaviridae, MESH : Nerve Tissue Proteins, MESH : Toluene, Cell Line, Transformed, bcl-2-Associated X Protein, Mitochondria, MESH : Epithelial Cells, medicine.anatomical_structure, MESH: Cell Transformation, Viral, MESH: Enzyme Inhibitors, Female, MESH : Mitochondria, MESH : DNA, Neoplasm, MESH : Mutation, medicine.drug, MESH: Mutation, MESH: Cell Line, Tumor, MESH: Thiazoles, MESH: DNA, Neoplasm, Nerve Tissue Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Line, Tumor, medicine, MESH: bcl-2-Associated X Protein, Benzothiazoles, MESH: Cell Line, Transformed, MESH : Papillomaviridae, 030304 developmental biology, MESH : Enzyme Inhibitors, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH: Transcription, Genetic, Biochemistry (medical), Wild type, Membrane Proteins, MESH : Transcription, Genetic, Cell Biology, Cell Transformation, Viral, biology.organism_classification, Molecular biology, MESH: Hela Cells, MESH : Tumor Suppressor Protein p53, MESH: Staurosporine, Tumor Suppressor Protein p53, Toluene
Abstract: International audience; We recently argued for a major role of p53 in staurosporine(ST)-induced apoptosis of immortalized epithelial cells, depending on their p53 status. Here, we studied the effects of PRIMA-1 (p53 reactivation and induction of massive apoptosis) and Pifithrin-alpha (p fifty-three inhibitor) in combination with ST to reinforce our previous results by respectively restoring or inhibiting the p53 transcriptional activity in different cell lines.PRIMA-1 does modify neither expression of apoptosis-related proteins nor the percentage of wild-type p53 HeLa and CaSki cells with [symbol: see text]delta psi m and DNA cleavage, whilst it increases by 45% Bax expression and apoptosis of mutated p53 C33A cells. Pifithrin-alpha, does modify neither Bax expression nor apoptosis level of C33A cells, but readily inhibits both [symbol: see text]delta psi m and DNA fragmentation of p53wt cells with decreasing Bax expression. These data support the evidence that PRIMA-1 could be a good candidate, as an anti-cancer drug targeting mutant p53, in order to increase ST efficiency. Moreover, Pifithrin-alpha could be used in combination with ST and PRIMA-1 to prevent side effects of anti-tumor therapies in cells expressing mutant P53.
Published: 2006
Full Text: View/download PDF

33. Identification and expression of a new splicing variant of FAD-sulfhydryl oxidase in adult rat brain

Author: Michèle Jouvenot, Dominique Fellmann, Franck Thiebault, Georges Mairet-Coello, Didier Colin, Jean Radom, Mai J. Dognin-Bergeret, Annick Esnard-Fève, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Estrogènes, Expression génique et pathologies du Système Nerveux Central - UFC ( E2SNC / ESTROGENES ), Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Estrogènes, Expression génique et pathologies du Système Nerveux Central - UFC (E2SNC / ESTROGENES), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Protein isoform, Male, Glycosylation, MESH : Molecular Sequence Data, MESH : RNA, Messenger, Transcription, Genetic, Gene Expression, MESH : Alternative Splicing, MESH: Amino Acid Sequence, MESH: Rats, Sprague-Dawley, Biochemistry, Rats, Sprague-Dawley, 0302 clinical medicine, Structural Biology, MESH: Animals, Cerebral Cortex, 0303 health sciences, Genome, MESH : Rats, MESH: Alternative Splicing, MESH : Amino Acid Sequence, MESH : Glycosylation, Brain, MESH: Glycosylation, MESH : Oxidoreductases, MESH: Flavin-Adenine Dinucleotide, RNA splicing, Flavin-Adenine Dinucleotide, MESH : Cerebral Cortex, Thioredoxin, Oxidoreductases, Signal peptide, MESH: Gene Expression, MESH: Rats, Immunoprecipitation, MESH : Male, Molecular Sequence Data, Biophysics, Biology, MESH : Immunoprecipitation, 03 medical and health sciences, MESH: Brain, Complementary DNA, Genetics, Animals, MESH: Genome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Flavin-Adenine Dinucleotide, MESH: Oxidoreductases, Amino Acid Sequence, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: RNA, Messenger, MESH: Molecular Sequence Data, MESH: Immunoprecipitation, MESH: Transcription, Genetic, Alternative splicing, MESH : Transcription, Genetic, Molecular biology, MESH: Male, MESH: Cerebral Cortex, MESH : Rats, Sprague-Dawley, Rats, MESH : Gene Expression, Open reading frame, Alternative Splicing, MESH : Brain, MESH : Animals, MESH : Genome, 030217 neurology & neurosurgery
Abstract: Flavoproteins of the quiescin/sulfhydryl oxidase (QSOX) family catalyze oxidation of peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide. We report here the molecular cloning of a new putative sulfhydryl oxidase cDNA, rQSOX-L (GenBank Accession no AY623665 ), from adult rat brain and its expression studied by RT-PCR, Northern and Western blots in rat tissues. DNA-sequencing demonstrated the existence of two cDNAs in rat cortex, corresponding to a long transcript ( rQSOX-L ) and a short transcript ( rQSOX-S ) which differed by 851 nucleotides due to alternative splicing. The new transcript, rQSOX-L (3356 nucleotides), was specifically expressed in brain, hypophysis, heart, testis and seminal vesicle. The distribution of this variant is not homogeneous in the different tissues studied and suggests a complex gene regulation. The full-length rQSOX-L cDNA has an open reading frame of 2250-bp encoding a protein of 750 amino acids that contains a signal peptide sequence, a protein-disulfide-isomerase-type thioredoxin and ERV1-ALR domains and a long form specific C-terminal extension. The rQSOX-L protein is highly homologous to members of the sulfhydryl oxidase/Quiescin family and contains particularly two potential sites for N -glycosylation. This protein isoform was specifically detected in rat brain tissues in opposition to the low molecular form that was ubiquitous. Matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis of the immunoprecipitate tryptic fragments allowed the identification of rQSOX-L protein.
Published: 2006
Full Text: View/download PDF

34. Selection of single-chain antibodies that specifically interact with vesicular stomatitis virus (VSV) nucleocapsid and inhibit viral RNA synthesis

Author: Denis Gerlier, Jean-Claude Cortay, Frédéric Iseni, Virologie et pathogenèse virale ( VPV ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Virologie et Pathologie Humaine ( VirPath ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Virologie et Pathologie Humaine (VirPath), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Molecular Sequence Data, Transcription, Genetic, viruses, MESH: Amino Acid Sequence, Antibodies, Viral, scFv, in vitro virus transcription, MESH: Recombinant Proteins, Epitopes, chemistry.chemical_compound, Antibody Specificity, Transcription (biology), RNA polymerase, single chain antibody, OCIS 000.1430, Immunoglobulin Fragments, Polymerase, nucleoprotein, MESH : Antibody Specificity, MESH : Amino Acid Sequence, Recombinant Proteins, MESH : Immunoglobulin Fragments, Vesicular stomatitis virus, VSV, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH : Antibodies, Viral, MESH : Vesicular stomatitis-Indiana virus, MESH: Epitopes, MESH: Vesicular stomatitis-Indiana virus, MESH : Recombinant Proteins, MESH: Nucleocapsid, Molecular Sequence Data, RNA-dependent RNA polymerase, Biology, MESH : Epitopes, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vesicular stomatitis Indiana virus, Peptide Library, MESH : Peptide Library, Virology, MESH : RNA, Viral, Amino Acid Sequence, MESH: Antibody Specificity, Nucleocapsid, MESH: Immunoglobulin Fragments, MESH: Molecular Sequence Data, MESH: Transcription, Genetic, RNA, MESH : Transcription, Genetic, Rhabdoviridae, biology.organism_classification, Nucleoprotein, MESH : Nucleocapsid, chemistry, biology.protein, MESH: Peptide Library, MESH: Antibodies, Viral
Abstract: International audience; The RNA genome of non-segmented negative-strand RNA viruses is completely covered by the nucleoprotein (N) forming a ribonucleoprotein complex, the nucleocapsid. The nucleocapsid functions as the template for viral RNA synthesis that is mediated by a viral RNA-dependent RNA polymerase. It is postulated that the selection of molecules that would specifically target the nucleocapsid and thus inhibit the viral polymerase activity could represent a common approach to block negative-strand RNA viruses. Two single-chain antibody fragments (scFv) that were selected using the phage display technology and interacted specifically with vesicular stomatitis virus (VSV) nucleocapsid were characterized. The two recombinant antibodies recognize a conformational epitope on the nucleocapsid and immunoprecipitate specifically nucleocapsids from infected cell extracts. Both antibodies have a strong inhibitory effect on VSV transcription activity in vitro. Thus, they represent starting molecules for future development of in vivo viral RNA synthesis inhibitors.
Published: 2006
Full Text: View/download PDF

35. Transcriptional analysis of the cyclopropane fatty acid synthase gene of Lactococcus lactis MG1363 at low pH

Author: S. Dusko Ehrlich, Yanick Auffray, Emmanuelle Maguin, AurÃ©lie Budin-Verneuil, Vianney Pichereau, Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, 1Génétique Microbienne, INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, Institut National de la Recherche Agronomique (INRA), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Génétique Microbienne (UGM), Laboratoire de Microbiologie de l’Environnement (LME), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Risques Microbiens ( U2RM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Institut National de la Recherche Agronomique ( INRA ), Laboratoire des Sciences de l'Environnement Marin (LEMAR) ( LEMAR ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Brest ( UBO ) -Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ) -Institut Universitaire Européen de la Mer ( IUEM ), Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ), and Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN)
Subjects: MESH: Hydrogen-Ion Concentration, MESH : Molecular Sequence Data, CLYCOPROPANE FATTY ACID SYNTHASE, Transcription, Genetic, MESH : Operon, Operon, [SDV]Life Sciences [q-bio], Mutant, MESH : Promoter Regions, Genetic, RECOMBINANT FUSION PROTEIN, MESH: Base Sequence, medicine.disease_cause, MESH : Ligases, Ligases, Plasmid, Genes, Reporter, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Lactic acid bacteria, Fatty acid modification, MESH: Up-Regulation, MESH : DNA, Bacterial, Promoter Regions, Genetic, MESH : Up-Regulation, MESH : Adaptation, Physiological, MESH : Methyltransferases, Regulation of gene expression, TRANSCRITIONAL ANALYSIS, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, biology, INDUCTION, MESH: Gene Expression Regulation, Enzymologic, MESH : beta-Galactosidase, Hydrogen-Ion Concentration, MESH : Genes, Reporter, Adaptation, Physiological, Up-Regulation, MESH: beta-Galactosidase, Fatty acid synthase, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, MESH: Ligases, MESH: Methionine Adenosyltransferase, Acid stress, MESH : Gene Expression Regulation, Bacterial, DNA, Bacterial, MESH: Operon, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Molecular Sequence Data, ACIDITY, Microbiology, Gene Expression Regulation, Enzymologic, MESH : Gene Expression Regulation, Enzymologic, MESH : Methionine Adenosyltransferase, TRANSCRIPTIONAL ANALYSIS, 03 medical and health sciences, MESH : Hydrogen-Ion Concentration, MESH: Methyltransferases, MESH: Promoter Regions, Genetic, Genetics, medicine, MESH: Recombinant Fusion Proteins, LACTOCOCCUS LACTIS, Northern blot, Molecular Biology, Escherichia coli, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, MESH: Transcription, Genetic, GENE EXPRESSION REGULATION, Lactococcus lactis, MESH: Genes, Reporter, MESH : Transcription, Genetic, Gene Expression Regulation, Bacterial, Methionine Adenosyltransferase, Methyltransferases, beta-Galactosidase, biology.organism_classification, Molecular biology, MESH: Adaptation, Physiological, MESH: DNA, Bacterial, MESH: Lactococcus lactis, biology.protein, MESH : Base Sequence, MESH : Lactococcus lactis
Abstract: International audience; Cyclopropane fatty acid synthase (cfa) catalyses the transfer of a methyl group from S-adenosylmethionine (SAM) to unsaturated fatty acids. Northern blot experiments demonstrated that the Lactococcus lactis MG1363 cfa gene is mainly expressed as a bicistronic transcript together with metK, the gene encoding SAM synthetase, and is highly induced by acidity. The cfa promoter was characterized by 5'-RACE PCR, and fused to beta-galactosidase by cloning into the pAK80 plasmid. This transcriptional fusion was highly induced by acidity (23-fold at pH 5) as well as during entry into the stationary phase (8-fold) in L. lactis. Interestingly, the cfa promoter expression is repressed in a L. lactis relA* mutant which accumulates (p)ppGpp, whereas its induction by acidity appeared independent of (p)ppGpp in L. lactis and in Escherichia coli.
Published: 2005
Full Text: View/download PDF

36. CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence

Author: Marie-Cécile, Lamy, Mohammed, Zouine, Juliette, Fert, Massimo, Vergassola, Elisabeth, Couve, Elisabeth, Pellegrini, Philippe, Glaser, Frank, Kunst, Tarek, Msadek, Patrick, Trieu-Cuot, Claire, Poyart, Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Bactériologie, CHU Cochin [AP-HP], Génomique des Microorganismes Pathogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by research funds from the Institut National de la Santé et de la Recherche Médicale, the European Commission (Grant QLG2‐CT‐1999‐01455), the Centre National de la Recherche Scientifique, the Institut Pasteur (PTR No. 17 and GPH No. 9), and the Universities Paris 5 and Paris 7. M.‐C. Lamy was supported by the Ministère de la Recherche et des Technologies and the Fondation pour la Recherche Médicale., We are grateful to J.L. Berretti for determination of haemolytic activities, D. Euphrasie for help in the construction of the ΔCylE mutant, and S. Dubrac and C. Buchrieser for helpful discussion., and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH : Virulence Factors, MESH : Hemolysis, Transcription, Genetic, MESH : Operon, MESH : Streptococcal Infections, MESH : Gene Deletion, MESH: Virulence, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Adhesion, Hemolysin Proteins, MESH: Streptococcal Infections, MESH : Bacterial Proteins, MESH: Animals, Promoter Regions, Genetic, MESH: Bacterial Proteins, MESH: Gene Expression Regulation, Bacterial, Virulence, MESH : Rats, MESH : Genes, Bacterial, MESH : Virulence, MESH : Streptococcus agalactiae, MESH: Hemolysis, MESH : Epithelial Cells, MESH: Promoter Regions (Genetics), MESH: Hemolysin Proteins, MESH: Repressor Proteins, MESH: Epithelial Cells, MESH: Regulon, MESH: Genes, Bacterial, MESH : Repressor Proteins, Signal Transduction, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, MESH: Rats, Virulence Factors, MESH : Bacterial Adhesion, MESH : Regulon, MESH : Hemolysin Proteins, MESH : Protein Kinases, Hemolysis, Regulon, Streptococcus agalactiae, Lethal Dose 50, MESH: Gene Expression Profiling, Bacterial Proteins, Streptococcal Infections, Operon, Animals, Humans, MESH : Lethal Dose 50, MESH: Bacterial Adhesion, MESH: Protein Kinases, MESH: Virulence Factors, MESH : Signal Transduction, MESH: Humans, Gene Expression Profiling, MESH: Transcription, Genetic, MESH : Gene Expression Profiling, MESH : Humans, MESH : Transcription, Genetic, Epithelial Cells, Gene Expression Regulation, Bacterial, MESH: Streptococcus agalactiae, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Promoter Regions (Genetics), MESH : Disease Models, Animal, Rats, Repressor Proteins, Disease Models, Animal, MESH: Lethal Dose 50, Genes, Bacterial, MESH: Gene Deletion, MESH : Animals, MESH: Disease Models, Animal, Protein Kinases, Gene Deletion
Abstract: International audience; In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR. A DeltacovSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar. Adherence of the DeltacovSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions. However, the DeltacovSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired. A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD(50) of the mutant strain was observed in the neonate rat sepsis model. The pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses.
Published: 2004
Full Text: View/download PDF

37. The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity

Author: Marc Piechaczyk, Jean-Michel Mesnard, Charlotte Arpin, Gilles Gaudray, Christian Devaux, Jihane Basbous, Infections rétrovirales et signalisation cellulaire ( IRSC ), Université Montpellier 1 ( UM1 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), ARC, Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Transcription, Genetic, MESH : Hela Cells, Proto-Oncogene Proteins c-jun, Retroviridae Proteins, MESH: Streptavidin, MESH : Blotting, Western, Biochemistry, MESH: Down-Regulation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Transcription (biology), Genes, Reporter, MESH: Gene Products, tax, MESH : Trans-Activation (Genetics), MESH: Animals, MESH : Viral Proteins, 0303 health sciences, c-jun, MESH : Protein Binding, MESH: Transcription Factors, MESH : beta-Galactosidase, MESH : Precipitin Tests, MESH : Human T-lymphotropic virus 1, MESH: Transcription Factor AP-1, MESH: Leucine Zippers, 3. Good health, MESH: COS Cells, MESH: Promoter Regions (Genetics), Basic-Leucine Zipper Transcription Factors, MESH : Transcription Factor AP-1, 030220 oncology & carcinogenesis, COS Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, JunB, MESH : Protein Structure, Tertiary, MESH : Proto-Oncogene Proteins c-jun, Transcriptional Activation, MESH : Glutathione Transferase, Blotting, Western, Biotin, Down-Regulation, MESH: Basic-Leucine Zipper Transcription Factors, Transfection, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, Viral Proteins, MESH : Basic-Leucine Zipper Transcription Factors, Humans, MESH: Protein Binding, MESH: Blotting, Western, Collagenases, E2F, Molecular Biology, MESH: Glutathione Transferase, MESH: Human T-lymphotropic virus 1, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, MESH: Genes, Reporter, MESH : Humans, Precipitin Tests, MESH : Promoter Regions (Genetics), Protein Structure, Tertiary, MESH : Streptavidin, Microscopy, Fluorescence, MESH: Binding Sites, HTLV-1, MESH: Luciferases, HeLa Cells, Transcription Factors, Time Factors, MESH : Transcription Factors, MESH : Microscopy, Fluorescence, MESH : DNA, Complementary, MESH: Collagenases, MESH: Microscopy, Fluorescence, MESH : Biotin, MESH : Down-Regulation, Transactivation, hemic and lymphatic diseases, MESH : RNA, MESH: Precipitin Tests, Luciferases, Promoter Regions, Genetic, Glutathione Transferase, Human T-lymphotropic virus 1, MESH : Collagenases, Gene Products, tax, MESH : Genes, Reporter, MESH: beta-Galactosidase, MESH : Dimerization, MESH: Genome, Viral, MESH : Transfection, MESH : COS Cells, Dimerization, MESH : Genome, Viral, Protein Binding, MESH : Time Factors, Leucine zipper, DNA, Complementary, JUNB, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genome, Viral, Biology, MESH: Two-Hybrid System Techniques, MESH: RNA, Two-Hybrid System Techniques, MESH: Biotin, Animals, Transcription factor, 030304 developmental biology, MESH : Luciferases, Leucine Zippers, Binding Sites, Activator (genetics), MESH : Gene Products, tax, MESH: Transcription, Genetic, MESH: Transfection, MESH: Time Factors, c-Jun, MESH : Transcription, Genetic, Cell Biology, MESH: DNA, Complementary, beta-Galactosidase, AP-1, Molecular biology, MESH: Viral Proteins, Transcription Factor AP-1, MESH: Hela Cells, MESH: Dimerization, MESH : Two-Hybrid System Techniques, MESH: Trans-Activation (Genetics), RNA, MESH : Leucine Zippers, Streptavidin, MESH : Animals, MESH : Binding Sites
Abstract: The human T-cell leukemia virus type I (HTLV-I)-encoded Tax protein activates transcription from the viral promoter via association with the cellular basic leucine zipper factor cAMP-response element-binding protein-2. Tax is also able to induce cellular transformation of T lymphocytes probably by modulating transcriptional activity of cellular factors, including nuclear factor-kappaB, E2F, activator protein-1 (AP-1), and p53. Recently, we characterized in HTLV-I-infected cells the presence of a novel viral protein, HBZ, encoded by the complementary strand of the HTLV-I RNA genome (Gaudray, G., Gachon, F., Basbous, J., Biard-Piechaczyk, M., Devaux, C., and Mesnard, J.-M. (2002) J. Virol. 76, 12813-12822). HBZ is a nuclear basic leucine zipper protein that down-regulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter. In searching for other cellular targets of HBZ, we identified two members of the Jun family, JunB and c-Jun. Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun. When transiently introduced into CEM cells with a reporter gene containing the AP-1 site from the collagenase promoter, HBZ suppressed transactivation by c-Jun. On the other hand, the combination of HBZ with Jun-B had higher transcriptional activity than JunB alone. Consistent with the structure of its basic domain, we demonstrate that HBZ decreases the DNA-binding activity of c-Jun and JunB. Last, we show that c-Jun is no longer capable of activating the basal expression of the HTLV-I promoter in the presence of HBZ in vivo. Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax.
Published: 2003
Full Text: View/download PDF

38. AMP-activated protein kinase and hepatic genes involved in glucose metabolism

Author: Dalila Azzout-Marniche, Pascal Ferré, Fabienne Foufelle, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Azzout-Marniche, Dalila
Subjects: MESH : RNA, Messenger, Transcription, Genetic, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], AMP-Activated Protein Kinases, Mitogen-activated protein kinase kinase, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Multienzyme Complexes, Biochemistry, MAP2K7, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ASK1, MESH: Animals, MESH: AMP-Activated Protein Kinases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Gene Expression Regulation, Enzymologic, MESH : AMP-Activated Protein Kinases, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH : Multienzyme Complexes, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glucose, Liver, 030220 oncology & carcinogenesis, MESH : Protein-Serine-Threonine Kinases, MESH: Enzyme Activation, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein Serine-Threonine Kinases, Biology, Gene Expression Regulation, Enzymologic, MESH: Protein-Serine-Threonine Kinases, MESH : Gene Expression Regulation, Enzymologic, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], 03 medical and health sciences, Multienzyme Complexes, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, RNA, Messenger, c-Raf, Protein kinase A, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, MESH : Glucose, MESH: Transcription, Genetic, MESH : Humans, Cyclin-dependent kinase 2, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Liver, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein kinase R, Enzyme Activation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Glucose, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], biology.protein, Cyclin-dependent kinase 9, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Liver
Abstract: International audience; Mammalian AMP-activated protein kinase presents strong structural and functional similarities with the yeast sucrose non-fermenting 1 (Snf1) kinase involved in the derepression of glucose-repressed genes. It is now clearly established that AMP-activated protein kinase in the liver decreases glycolytic/lipogenic gene expression as well as genes involved in hepatic glucose production. This is achieved through a decreased transcriptional efficiency of transcription factors such as sterol-regulatory-element-binding protein-1c, carbohydrate-response-element-binding protein, hepatocyte nuclear factor 4 alpha or forkhead-related protein. Clearly, the long-term consequences of AMP-activated protein kinase activation have to be taken into account if activators of this enzyme are to be designed as anti-diabetic drugs.
Published: 2003
Full Text: View/download PDF

39. Interleukin-1beta induces glycosaminoglycan synthesis via the prostaglandin E2 pathway in cultured human cervical fibroblasts

Author: Michelle Breuiller-Fouché, Françoise Ferré, Thomas Schmitz, Dominique Cabrol, Emmanuelle Dallot, Marie-Josèphe Leroy, Breuiller-Fouche, Michelle, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Génomique et épigénétique des pathologies placentaires ( Inserm U709 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: MESH : RNA, Messenger, Transcription, Genetic, medicine.medical_treatment, MESH: Sulfonamides, Cervix Uteri, MESH: Base Sequence, 0302 clinical medicine, Cells, Cultured, Glycosaminoglycans, MESH : Isoenzymes, Sulfonamides, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Dinoprostone, MESH: Cervix Uteri, Receptors, Prostaglandin E, EP3 Subtype, MESH : Biphenyl Compounds, MESH : DNA Primers, MESH: Membrane Proteins, Prostaglandin E, MESH: Cells, Cultured, MESH: DNA Primers, medicine.medical_specialty, MESH : Cyclooxygenase 2, MESH: Prostaglandin-Endoperoxide Synthases, Dinoprostone, Article, 03 medical and health sciences, MESH: Cyclooxygenase Inhibitors, MESH : Fibroblasts, Genetics, Humans, Cyclooxygenase Inhibitors, RNA, Messenger, Molecular Biology, Nitrobenzenes, MESH: Humans, Cyclooxygenase 2 Inhibitors, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Biphenyl Compounds, MESH : Humans, MESH: Interleukin-1, Fibroblasts, Receptors, Prostaglandin E, EP2 Subtype, MESH : Nitrobenzenes, Endocrinology, Reproductive Medicine, MESH : Membrane Proteins, MESH: Female, Developmental Biology, Embryology, MESH: Cyclooxygenase 2 Inhibitors, MESH: Receptors, Prostaglandin E, MESH : Cyclooxygenase 2 Inhibitors, MESH : Female, Prostaglandin E2, Receptor, MESH : Prostaglandin-Endoperoxide Synthases, MESH: Kinetics, Obstetrics and Gynecology, Interleukin, MESH: Glycosaminoglycans, MESH : Cyclooxygenase Inhibitors, Receptor antagonist, Receptors, Prostaglandin E, EP1 Subtype, Isoenzymes, MESH: Isoenzymes, lipids (amino acids, peptides, and proteins), Female, Signal transduction, MESH : Kinetics, MESH: Cyclooxygenase 2, MESH : Receptors, Prostaglandin E, MESH: Biphenyl Compounds, medicine.drug, MESH : Dinoprostone, medicine.drug_class, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Interleukin-1, Paracrine signalling, Internal medicine, MESH : Cells, Cultured, medicine, MESH : Glycosaminoglycans, Receptors, Prostaglandin E, Autocrine signalling, MESH : Sulfonamides, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, DNA Primers, 030304 developmental biology, MESH: RNA, Messenger, Base Sequence, MESH: Transcription, Genetic, Membrane Proteins, MESH : Transcription, Genetic, MESH: Nitrobenzenes, Cell Biology, Kinetics, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, MESH: Fibroblasts, MESH : Cervix Uteri, MESH : Base Sequence, Receptors, Prostaglandin E, EP4 Subtype, Interleukin-1
Abstract: International audience; The aim of this study was to identify, in cultured human cervical fibroblasts, the mechanisms by which interleukin (IL)-1beta induces the synthesis of glycosaminoglycans (GAG) and to explore the putative role of prostaglandin E(2) (PGE(2)) in this process. Exposure of the cells for 24 h to IL-1beta induced a significant (P < 0.05) dose-dependent increase in GAG synthesis. IL-1beta (1 ng/ml) induced the expression of cyclooxygenase-2 (COX-2) protein 6 h after treatment, accompanied by a 7.5-fold increase in PGE(2) production. We confirmed that NS398, a selective COX-2 inhibitor, dose-dependently blocked PGE(2) augmentation following IL-1beta treatment. AH23848, the selective EP(4) receptor antagonist, completely abolished IL-1beta-induced GAG synthesis, whereas AH6809, an EP(2) receptor antagonist, had no effect on the stimulatory effects of IL-1beta. Furthermore, we demonstrated that 6 h exposure to IL-1beta induced a notable increase in EP(4) receptor mRNA expression and a decrease in EP(1) receptor mRNA but had no effect on the expression of EP(2) and EP(3) receptor transcripts. In conclusion, these findings indicate that IL-1beta not only induced GAG synthesis by increasing COX-2 protein expression and the subsequent PGE(2) production but also enhanced the responsiveness of cervical fibroblasts to PGE(2) by selectively up-regulating EP(4) receptor mRNA expression. These results suggest that PGE(2) may regulate human cervical ripening in an autocrine/paracrine manner via EP(4) receptors.
Published: 2003

40. Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron

Author: Jean-Marc Latour, Daniè Le Touati, Benoît D'Autréaux, Isabelle Michaud-Soret, Beate Bersch, Laboratoire de Physico-chimie des Métaux en Biologie (LPCMB), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Résonance Magnétique Nucléaire (LRMN), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Biologie des Métaux (BioMet), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie structurale ( IBS - UMR 5075 ), BioMet, Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: MESH : Escherichia coli, Transcription, Genetic, Protein Conformation, medicine.disease_cause, MESH : Iron, chemistry.chemical_compound, Protein structure, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], iron, MESH: Protein Conformation, MESH : Bacterial Proteins, MESH: Bacterial Proteins, MESH : Protein Conformation, chemistry.chemical_classification, 0303 health sciences, MESH: Iron, Multidisciplinary, integumentary system, MESH: Escherichia coli, Nitrosylation, Biological Sciences, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, MESH : Electron Spin Resonance Spectroscopy, MESH : Nitric Oxide, MESH : Dimerization, MESH: Repressor Proteins, Aerobactin, MESH : Repressor Proteins, escherichia coli, transcription, Dimerization, medicine.drug, inorganic chemicals, Repressor, Biology, Cofactor, 03 medical and health sciences, Bacterial Proteins, nitric oxide, medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Escherichia coli, 030304 developmental biology, 030306 microbiology, metalloregulator, MESH: Transcription, Genetic, Electron Spin Resonance Spectroscopy, MESH : Transcription, Genetic, Repressor Proteins, Enzyme, chemistry, MESH: Dimerization, MESH: Nitric Oxide, biology.protein, Ferric, bacteria, MESH: Electron Spin Resonance Spectroscopy
Abstract: Ferric uptake regulation protein (Fur) is a bacterial global regulator that uses iron as a cofactor to bind to specific DNA sequences. The function of Fur is not limited to iron homeostasis. A wide variety of genes involved in various mechanisms such as oxidative and acid stresses are under Fur control. Flavohemoglobin (Hmp) is an NO-detoxifying enzyme induced by NO and nitrosothiol compounds. Fur recently was found to regulate hmp in Salmonella typhimurium , and in Escherichia coli , the iron-chelating agent 2,2′-dipyridyl induces hmp expression. We now establish direct inhibition of E. coli Fur activity by NO. By using chromosomal Fur-regulated lacZ reporter fusion in E. coli , Fur activity is switched off by NO at micromolar concentration. In vitro Fur DNA-binding activity, as measured by protection of restriction site in aerobactin promoter, is directly sensitive to NO. NO reacts with Fe II in purified FeFur protein to form a S = 1/2 low-spin FeFur–NO complex with a g = 2.03 EPR signal. Appearance of the same EPR signal in NO-treated cells links nitrosylation of the iron with Fur inhibition. The nitrosylated Fur protein is still a dimer and is stable in anaerobiosis but slowly decays in air. This inhibition probably arises from a conformational switch, leading to an inactive dimeric protein. These data establish a link between control of iron metabolism and the response to NO effects.
Published: 2002
Full Text: View/download PDF

41. The BTB/POZ domain of the regulatory proteins Bric à brac 1 (BAB1) and Bric à brac 2 (BAB2) interacts with the novel Drosophila TAF(II) factor BIP2/dTAF(II)155

Author: Jan Larsson, Jean-Christophe Pointud, Bernard Dastugue, Jean-Louis Couderc, Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of microbiology, Umeå University, Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Couderc, Jean-Louis
Subjects: MESH : Molecular Sequence Data, Time Factors, MESH : Transcription Factors, Transcription, Genetic, MESH: Drosophila, MESH : Models, Genetic, Plasma protein binding, MESH : Blotting, Western, MESH: Protein Structure, Tertiary, Protein structure, Transcription (biology), Transcriptional regulation, Drosophila Proteins, MESH: Animals, transcriptional regulation, MESH: Models, Genetic, BTB/POZ domain, TAFII, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics, MESH : Blotting, Northern, MESH : Protein Binding, MESH: Transcription Factors, DNA-Binding Proteins, MESH: Repressor Proteins, Drosophila, MESH : DNA-Binding Proteins, MESH : Repressor Proteins, MESH : Protein Structure, Tertiary, Drosophila Protein, MESH : Time Factors, Plasmids, Protein Binding, MESH: Drosophila Proteins, Blotting, Western, Molecular Sequence Data, Biology, MESH: Two-Hybrid System Techniques, Chromatin remodeling, MESH: Plasmids, Two-Hybrid System Techniques, [SDV.BDD] Life Sciences [q-bio]/Development Biology, MESH: Blotting, Northern, MESH: Blotting, Western, MESH: Protein Binding, Animals, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, MESH : Drosophila, Transcription factor, Molecular Biology, MESH: Molecular Sequence Data, Models, Genetic, MESH: Transcription, Genetic, MESH: Time Factors, MESH : Transcription, Genetic, Cell Biology, MESH : Drosophila Proteins, Blotting, Northern, Protein Structure, Tertiary, Repressor Proteins, MESH : Two-Hybrid System Techniques, MESH : Plasmids, MESH : Animals, MESH: DNA-Binding Proteins, Developmental Biology, Transcription Factors
Abstract: International audience; The BTB/POZ domain is an evolutionarily conserved protein-protein interaction domain present in the N-terminal region of numerous transcription factors involved in development, chromatin remodeling, and human cancers. This domain is involved in homomeric and heteromeric associations with other BTB/POZ domains. The Drosophila BTB/POZ proteins Bric ?rac 1 (BAB1) and Bric ?rac 2 (BAB2) are developmentally regulated transcription factors which are involved in pattern formation along the proximo-distal axis of the leg and antenna, in the morphogenesis of the adult ovaries, and in the control of sexually dimorphic characters. We have identified partners of the BAB1 protein by using the two-hybrid system. The characterization of one of these proteins, called BIP2 for BAB Interacting Protein 2, is presented. BIP2 is a novel Drosophila TATA-box Protein Associated Factor (TAF(II)), also named dTAF(II)155. We show that the BTB/POZ domains of BAB1 and BAB2 are sufficient to mediate a direct interaction with BIP2/dTAF(II)155. This provides a direct link between these BTB/POZ transcription factors and the basal transcriptional machinery. We discuss the implications of the interaction between a BTB/POZ domain and a TAF(II) for the molecular mechanisms of transcriptional control mediated by BTB/POZ transcription factors.
Published: 2001
Full Text: View/download PDF

42. Diffusible singlet oxygen as a probe of DNA deformation

Author: M, Buckle, A A, Travers, Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratory of Molecular Biology [Cambridge], Medical Research Council, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), and École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Autoradiography, MESH : Escherichia coli, MESH : Oxygen, Transcription, Genetic, MESH : DNA, MESH : Nucleic Acid Conformation, MESH : Singlet Oxygen, Diffusion, MESH: Autoradiography, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, Molecular Structure, Singlet Oxygen, MESH: Kinetics, MESH: Escherichia coli, MESH: DNA, MESH: Indicators and Reagents, DNA-Directed RNA Polymerases, MESH : Spectrophotometry, MESH: Promoter Regions (Genetics), MESH: Nucleic Acid Conformation, Spectrophotometry, MESH: Lasers, Electrophoresis, Polyacrylamide Gel, MESH : Kinetics, MESH: Oxygen, Photochemistry, Molecular Probe Techniques, MESH : Electrophoresis, Polyacrylamide Gel, MESH : Indicators and Reagents, MESH : DNA-Directed RNA Polymerases, MESH : Lasers, Escherichia coli, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Singlet Oxygen, Binding Sites, MESH: Spectrophotometry, Lasers, MESH: Transcription, Genetic, MESH : Transcription, Genetic, DNA, MESH : Promoter Regions (Genetics), MESH: DNA-Directed RNA Polymerases, Oxygen, Kinetics, Autoradiography, Nucleic Acid Conformation, Indicators and Reagents, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience
Published: 2001
Full Text: View/download PDF

43. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes

Author: Dalila Azzout-Marniche, Marc Foretz, Fabienne Foufelle, Pascal Ferré, Colette Guichard, Dominique Bécard, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: MESH: Protein Precursors, Transcription, Genetic, medicine.medical_treatment, MESH : Hepatocytes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Hepatocytes, 0302 clinical medicine, Insulin receptor substrate, Insulin, MESH: Animals, Enzyme Inhibitors, MESH : Immunoblotting, Cells, Cultured, Protein Synthesis Inhibitors, 0303 health sciences, MESH : Cell Nucleus, MESH : Glucokinase, MESH: Immunoblotting, food and beverages, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Glucokinase, MESH: Transcription Factors, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, MESH : DNA-Binding Proteins, Sterol Regulatory Element Binding Protein 1, MESH: Cells, Cultured, MESH: Cell Nucleus, MESH: Enzyme Activation, MESH : Cell Membrane, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Insulin, digestive system, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, MESH : Sterol Regulatory Element Binding Protein 1, MESH: Blotting, Northern, Protein Precursors, Molecular Biology, Dose-Response Relationship, Drug, Glucokinase, Endoplasmic reticulum, Cell Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sterol regulatory element-binding protein, Enzyme Activation, MESH: Phosphatidylinositol 3-Kinases, CCAAT-Enhancer-Binding Proteins, MESH: Female, Transcription Factors, MESH: Signal Transduction, Time Factors, MESH : Transcription Factors, MESH : Insulin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Dose-Response Relationship, Drug, Endoplasmic Reticulum, MESH: Dose-Response Relationship, Drug, Phosphatidylinositol 3-Kinases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], polycyclic compounds, MESH : Female, Cycloheximide, MESH: Cycloheximide, MESH : Protein Precursors, MESH : Endoplasmic Reticulum, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Blotting, Northern, DNA-Binding Proteins, Fatty acid synthase, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Enzyme Inhibitors, Female, lipids (amino acids, peptides, and proteins), MESH : Time Factors, Research Article, Signal Transduction, MESH: Rats, Immunoblotting, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Endoplasmic Reticulum, MESH : Cycloheximide, MESH : Cells, Cultured, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH : Protein Synthesis Inhibitors, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Protein Synthesis Inhibitors, MESH: Transcription, Genetic, MESH: Time Factors, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Phosphatidylinositol 3-Kinases, Cell Biology, Blotting, Northern, Rats, biology.protein, Hepatocytes, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, MESH: Cell Membrane
Abstract: International audience; The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of insulin on the transcription of genes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.
Published: 2000

44. Evidence for an uncommon alpha-actinin protein in Trichomonas vaginalis

Author: Gérard Coffe, Geneviève Bricheux, Guy Brugerolle, Nathalie Pradel, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Biologie des Protistes [Aubière] (LBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), BRICHEUX, Genevieve, and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Trichomonas vaginalis, MESH : Molecular Sequence Data, Transcription, Genetic, MESH : DNA, Complementary, Fluorescent Antibody Technique, MESH : Actins, MESH: Protein Structure, Secondary, MESH : Blotting, Western, Actinin, MESH: Amino Acid Sequence, MESH: Base Sequence, Protein Structure, Secondary, Homology (biology), MESH : Cytoskeleton, Protein sequencing, MESH: Actinin, Electrophoresis, Gel, Two-Dimensional, MESH: Animals, Peptide sequence, MESH: Fluorescent Antibody Technique, Cytoskeleton, MESH : Consensus Sequence, MESH : Sequence Alignment, MESH : Amino Acid Sequence, MESH : Blotting, Northern, [ SDV.MP.PRO ] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Actinin, alpha 1, Biochemistry, MESH: Calcium, MESH: 5' Untranslated Regions, Electrophoresis, Polyacrylamide Gel, DNA, Complementary, Blotting, Western, Molecular Sequence Data, MESH: Sequence Alignment, Sequence alignment, macromolecular substances, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Biology, MESH : Electrophoresis, Polyacrylamide Gel, MESH: Actins, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Consensus Sequence, Trichomonas vaginalis, Consensus sequence, MESH: Cytoskeleton, Animals, MESH: Blotting, Northern, MESH: Blotting, Western, Amino Acid Sequence, MESH: Consensus Sequence, MESH : Calcium, Molecular Biology, Actin, MESH: Molecular Sequence Data, Base Sequence, MESH: Transcription, Genetic, MESH : 5' Untranslated Regions, MESH : Transcription, Genetic, MESH : Electrophoresis, Gel, Two-Dimensional, MESH: DNA, Complementary, MESH : Trichomonas vaginalis, Blotting, Northern, MESH: Electrophoresis, Gel, Two-Dimensional, Molecular biology, Actins, MESH : Fluorescent Antibody Technique, Calcium, MESH : Base Sequence, Parasitology, MESH : Protein Structure, Secondary, MESH : Animals, 5' Untranslated Regions, Sequence Alignment, MESH : Actinin, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience; As part of our ongoing project of identification of actin-binding proteins implicated in the cell transition (flagellate to amoeboid/adherent) of Trichomonas vaginalis, we have characterized an alpha-actinin-related protein in this parasite. The protein (P100) has a molecular mass of 100 kDa and an isoelectric point of 5.5. A monoclonal antibody raised against this protein co-localizes with the actin network. P100 gene transcripts are co-expressed with actin throughout the cell cycle. Analysis of the deduced protein sequence reveals three domains: an N-terminal actin-binding region; a central region rich in alpha-helix; and a C-terminal domain with Ca(2+)-binding capacity. Whereas the N- and C-terminal regions are well-conserved as compared to other alpha-actinins, we observe in the central region an atypical distribution of residues in five repeats. The sequence of the repeats does not show any homology with the rod domain of the other alpha-actinins, except for the first repeat which shows some similarity. The four other repeats of T. vaginalis P100 appear to result from a duplication event which is not detectable in the other sequences.
Published: 1998

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

44 results on '"MESH : Transcription, Genetic"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources