19 results on '"Akiyama, Tetsu"'
Search Results
2. The RNA-binding protein Mex-3B plays critical roles in the development of steroid-resistant neutrophilic airway inflammation.
- Author
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Yamazumi Y, Sasaki O, Suyama-Fuchino S, Kohu K, Kamoshida Y, Harada H, Fujio K, Oda T, and Akiyama T
- Subjects
- Animals, Antibodies immunology, Antigen-Antibody Reactions, Asthma drug therapy, Asthma metabolism, Chemokine CXCL2 immunology, Female, Inflammation metabolism, Mice, Mice, Inbred BALB C, Mice, Knockout, Neutrophils metabolism, Oligonucleotides pharmacology, RNA-Binding Proteins antagonists & inhibitors, Drug Resistance drug effects, Inflammation drug therapy, Neutrophils drug effects, RNA-Binding Proteins metabolism, Steroids pharmacology
- Abstract
While most asthma can be treated with steroids, about 10%, called severe asthma, is refractory to steroids. It has recently been shown that in a subgroup of severe asthma cases, neutrophils that infiltrate into the airways play an important role in inflammation. However, the mechanisms underlying this increased neutrophil infiltration are not well understood. Here, using a mouse model of steroid-resistant neutrophilic inflammation, we show that mice deficient for the RNA-binding protein Mex-3B have significantly less neutrophil infiltration in the airways than wild-type mice. We further demonstrate that Mex-3B post-transcriptionally upregulates CXCL2, a chemokine that induces neutrophil chemotaxis and migration. Moreover, we show that treatment with either anti-CXCL2 antibody or anti-Mex-3B antisense oligonucleotide suppresses neutrophilic allergic airway inflammation. These results suggest that Mex-3B-mediated induction of CXCL2 is crucial for steroid-resistant neutrophilic allergic airway inflammation. Our findings suggest new strategies for therapeutic intervention in steroid-resistant severe asthma., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
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3. SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity.
- Author
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Hiraoka K, Hayashi T, Kaneko R, Nasu-Nishimura Y, Koyama-Nasu R, Kawasaki Y, and Akiyama T
- Subjects
- Brain Neoplasms pathology, Cell Line, Tumor, Gene Knockdown Techniques, Glioblastoma pathology, Humans, Receptors, G-Protein-Coupled genetics, SOX9 Transcription Factor genetics, Brain Neoplasms metabolism, Glioblastoma metabolism, Receptors, G-Protein-Coupled physiology, SOX9 Transcription Factor physiology, Up-Regulation physiology
- Abstract
LGR5 plays an important role in the self-renewal of stem cells and is used as a marker identifying self-renewing stem cells in small intestine and hair follicles. Moreover, LGR5 has been reported to be overexpressed in several cancers. SOX9 is a transcription factor that plays a key role in development, differentiation and lineage commitment in various tissues. It has also been reported that SOX9 is overexpressed in a variety of cancers and contributes to their malignant phenotype. Here we show that LGR5 is required for the tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in glioblastoma cells and directly enhances the expression of LGR5. We also demonstrate that knockdown of SOX9 suppresses the proliferation and tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated transcriptional regulation of LGR5 is critical for the tumorigenicity of glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a potentially promising target for the therapy of glioblastoma., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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4. Thr160 of Axin1 is critical for the formation and function of the β-catenin destruction complex.
- Author
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Koyama-Nasu R, Hayashi T, Nasu-Nishimura Y, Akiyama T, and Yamanaka R
- Subjects
- Adenomatous Polyposis Coli Protein chemistry, Adenomatous Polyposis Coli Protein metabolism, Axin Protein genetics, Binding Sites, Biomimetic Materials chemistry, Biomimetic Materials metabolism, Casein Kinase I chemistry, Casein Kinase I metabolism, Cell Line, Tumor, Glioblastoma metabolism, Glycogen Synthase Kinase 3 chemistry, Glycogen Synthase Kinase 3 metabolism, HEK293 Cells, Humans, Low Density Lipoprotein Receptor-Related Protein-5 antagonists & inhibitors, Low Density Lipoprotein Receptor-Related Protein-5 genetics, Low Density Lipoprotein Receptor-Related Protein-5 metabolism, Low Density Lipoprotein Receptor-Related Protein-6 antagonists & inhibitors, Low Density Lipoprotein Receptor-Related Protein-6 genetics, Low Density Lipoprotein Receptor-Related Protein-6 metabolism, Mutagenesis, Site-Directed, Phosphorylation, Protein Stability, RNA, Small Interfering genetics, Threonine chemistry, Wnt Signaling Pathway, beta Catenin chemistry, beta Catenin metabolism, Axin Protein chemistry, Axin Protein metabolism, Axin Signaling Complex chemistry, Axin Signaling Complex metabolism
- Abstract
Upon binding of a Wnt ligand to the frizzled (FZD)-low density lipoprotein receptor related protein 5/6 (LRP5/6) receptor complex, the β-catenin destruction complex, composed of Axin1, adenomatous polyposis coli (APC), glycogen synthase kinase 3 (GSK3) and casein kinase 1 (CK1), is immediately inactivated, which causes β-catenin stabilization. However, the molecular mechanism of signal transduction from the receptor complex to the β-catenin destruction complex is controversial. Here we show that Wnt3a treatment promotes the dissociation of the Axin1-APC complex in glioblastoma cells cultured in serum-free medium. Experiments with the GSK3 inhibitor BIO suggest that Axin1-APC dissociation was controlled by phosphorylation. Introduction of a phosphomimetic mutation into Thr160 of Axin1, located in the APC-binding region RGS, abrogated the interaction of Axin1 with APC. Consistent with these observations, the Axin1 phosphomimetic mutant lost the ability to reduce β-catenin stability and to repress β-catenin/TCF-dependent transcription. Taken together, our results suggest a novel mechanism of Wnt signaling through the dissociation of the β-catenin destruction complex by Axin1 Thr160 modification., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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5. Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells.
- Author
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Sugimasa H, Taniue K, Kurimoto A, Takeda Y, Kawasaki Y, and Akiyama T
- Subjects
- Animals, Cell Cycle Proteins genetics, Cell Line, Tumor, Cell Proliferation genetics, Colonic Neoplasms genetics, Gene Expression Regulation, Neoplastic, Heterogeneous-Nuclear Ribonucleoprotein K genetics, Humans, Mice, Inbred BALB C, Mitosis, Promoter Regions, Genetic, Up-Regulation, Xenograft Model Antitumor Assays, Cell Cycle Proteins metabolism, Colonic Neoplasms pathology, Heterogeneous-Nuclear Ribonucleoprotein K metabolism
- Abstract
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. In addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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6. PCDH10 is required for the tumorigenicity of glioblastoma cells.
- Author
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Echizen K, Nakada M, Hayashi T, Sabit H, Furuta T, Nakai M, Koyama-Nasu R, Nishimura Y, Taniue K, Morishita Y, Hirano S, Terai K, Todo T, Ino Y, Mukasa A, Takayanagi S, Ohtani R, Saito N, and Akiyama T
- Subjects
- Animals, Apoptosis, Brain Neoplasms genetics, Cadherins antagonists & inhibitors, Cadherins genetics, Cell Line, Tumor, Cell Proliferation, Gene Knockdown Techniques, Glioblastoma genetics, Heterografts, Humans, Mice, Mice, Nude, Neoplasm Invasiveness, Oncogene Proteins antagonists & inhibitors, Oncogene Proteins genetics, Oncogene Proteins metabolism, Protocadherins, RNA Interference, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cadherins metabolism, Glioblastoma metabolism, Glioblastoma pathology
- Abstract
Protocadherin10 (PCDH10)/OL-protocadherin is a cadherin-related transmembrane protein that has multiple roles in the brain, including facilitating specific cell-cell connections, cell migration and axon guidance. It has recently been reported that PCDH10 functions as a tumor suppressor and that its overexpression inhibits proliferation or invasion of multiple tumor cells. However, the function of PCDH10 in glioblastoma cells has not been elucidated. In contrast to previous reports on other tumors, we show here that suppression of the expression of PCDH10 by RNA interference (RNAi) induces the growth arrest and apoptosis of glioblastoma cells in vitro. Furthermore, we demonstrate that knockdown of PCDH10 inhibits the growth of glioblastoma cells xenografted into immunocompromised mice. These results suggest that PCDH10 is required for the proliferation and tumorigenicity of glioblastoma cells. We speculate that PCDH10 may be a promising target for the therapy of glioblastoma., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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7. Crystal structure of the guanylate kinase domain from discs large homolog 1 (DLG1/SAP97).
- Author
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Mori S, Tezuka Y, Arakawa A, Handa N, Shirouzu M, Akiyama T, and Yokoyama S
- Subjects
- Animals, Binding Sites, Crystallography, X-Ray, Discs Large Homolog 1 Protein, Guanylate Kinases chemistry, Humans, Models, Molecular, Protein Conformation, Protein Interaction Domains and Motifs, Rats, Recombinant Proteins chemistry, Species Specificity, Adaptor Proteins, Signal Transducing chemistry, Membrane Proteins chemistry
- Abstract
Discs large homolog 1 (DLG1/SAP97) is involved in the development and regulation of neuronal and immunological synapses. DLG1 is a member of the membrane associated guanylate kinase (MAGUK) family of proteins, which function as molecular scaffolds. The C-terminal guanylate kinase (GK) domain of DLG1 binds peptides with a phosphorylated serine residue. In this study, we solved the crystal structure of the GK domain of human DLG1. The C-terminal tail of DLG1 is bound to the peptide-binding site of an adjacent symmetry-related DLG1 GK molecule. The binding direction of the C-terminal tail to the peptide-binding site is opposite to that of the phosphorylated LGN peptide in complex with the rat DLG1 GK domain. The C-terminal tail forms a 310 helix, which is also different from the conformation of the phosphorylated LGN peptide. Nevertheless, the side chain interactions of the C-terminal tail with the DLG1 GK domain are similar to those of the phosphorylated LGN peptide., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
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8. The transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes.
- Author
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Yamazumi Y, Kamiya A, Nishida A, Nishihara A, Iemura S, Natsume T, and Akiyama T
- Subjects
- Active Transport, Cell Nucleus, HeLa Cells, Humans, Nerve Tissue Proteins genetics, Nuclear Pore Complex Proteins genetics, RNA Interference, Nerve Tissue Proteins metabolism, Nuclear Pore metabolism, Nuclear Pore Complex Proteins metabolism
- Abstract
NDC1 is a transmembrane nucleoporin that is required for NPC assembly and nucleocytoplasmic transport. We show here that NDC1 directly interacts with the nucleoporin ALADIN, mutations of which are responsible for triple-A syndrome, and that this interaction is required for targeting of ALADIN to nuclear pore complexes (NPCs). Furthermore, we show that NDC1 is required for selective nuclear import. Our findings suggest that NDC1-mediated localization of ALADIN to NPCs is essential for selective nuclear protein import, and that abrogation of the interaction between ALADIN and NDC1 may be important for the development of triple-A syndrome.
- Published
- 2009
- Full Text
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9. Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis.
- Author
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Hasegawa Y, Satoh K, Iizuka-Kogo A, Shimomura A, Nomura R, Akiyama T, and Senda T
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Kidney embryology, Mice, Mice, Knockout, Repressor Proteins, Ureter embryology, Cell Cycle Proteins metabolism, Embryonic Development, Kidney abnormalities, Kidney metabolism, Morphogenesis, Transcription Factors metabolism, Ureter abnormalities, Ureter metabolism
- Abstract
ICAT, inhibitor of beta-catenin and T cell factor, or Ctnnbip1, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between beta-catenin and T cell factor. Some ICAT-deficient (ICAT-/-) embryos exhibit unilateral or bilateral renal agenesis. In this study, we investigated developmental processes in the ICAT-/- kidney. ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the metanephros of embryonic day E11.5-E13.5 wild-type (ICAT+/+) mouse. In the E12.5-ICAT-/- metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT+/+ metanephros. More apoptotic MM cells were detected in the ICAT-/- metanephros than in the ICAT+/+ metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis.
- Published
- 2007
- Full Text
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10. PH domain-mediated membrane targeting of Asef.
- Author
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Muroya K, Kawasaki Y, Hayashi T, Ohwada S, and Akiyama T
- Subjects
- Animals, Cell Line, Dogs, Hydrogen-Ion Concentration, Kidney, Protein Binding, Recombinant Proteins, Rho Guanine Nucleotide Exchange Factors, Transfection, Cell Membrane metabolism, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors metabolism, Phospholipids metabolism
- Abstract
The APC-associated guanine nucleotide exchange factor (GEF) Asef regulates cell morphology and migration. Asef contains a pleckstrin homology (PH) domain in addition to Dbl homology (DH), APC-binding (ABR), and Src homology 3 (SH3) domains. Here we show that the PH domain of Asef binds to phosphatidylinositol 3,4,5-trisphophate [PtdIns(3,4,5)P3] and targets Asef to the cell-cell adhesion sites in MDCK II cells. Furthermore, we demonstrate that overexpression of Asef in MDCK II cells results in increases in the amounts of E-cadherin and the actin filaments at the sites of cell-cell contact. These results suggest that Asef is targeted via its PH domain to the cell-cell adhesion sites and is involved in the regulation of cell adhesion.
- Published
- 2007
- Full Text
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11. The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1.
- Author
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Setogawa T, Shinozaki-Yabana S, Masuda T, Matsuura K, and Akiyama T
- Subjects
- AMP-Activated Protein Kinase Kinases, Adaptor Proteins, Signal Transducing, Animals, Cell Line, Chlorocebus aethiops, Humans, LIM Domain Proteins, Protein Binding, Transcriptional Activation, Tumor Suppressor Protein p53 physiology, Two-Hybrid System Techniques, Up-Regulation, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, DNA-Binding Proteins metabolism, GATA6 Transcription Factor metabolism, Homeodomain Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Transcription Factors metabolism
- Abstract
The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers syndrome and various sporadic cancers such as lung adenocarcinoma. We show here that LKB1 forms a complex with LMO4, GATA-6, and Ldb1, and enhances GATA-mediated transactivation in a kinase-dependent manner. We further demonstrate that LKB1 has the potential to induce p21 expression in collaboration with LMO4, GATA-6, and Ldb1 through the p53-independent mechanism. Our findings suggest that LKB1 regulates GATA-mediated gene expression and that this activity of LKB1 may be important for its tumor suppressor function.
- Published
- 2006
- Full Text
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12. A functional link between Disrupted-In-Schizophrenia 1 and the eukaryotic translation initiation factor 3.
- Author
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Ogawa F, Kasai M, and Akiyama T
- Subjects
- Cell Line, Gene Expression Regulation, Humans, Statistics as Topic, Cytoplasmic Granules metabolism, Eukaryotic Initiation Factor-3 metabolism, Kidney metabolism, Nerve Tissue Proteins metabolism, Neuroblastoma metabolism, RNA-Binding Proteins metabolism, Schizophrenia metabolism
- Abstract
Disrupted-In-Schizophrenia 1 (DISC1) was identified as a candidate gene for schizophrenia. DISC1 is disrupted by a balanced t(1;11)(q42.1;q14.3) translocation segregating with schizophrenia and related psychiatric illness in a large Scottish family. Here, we show that DISC1 interacts via its globular domain with the p40 subunit of the eukaryotic translation initiation factor 3. Furthermore, we found that overexpression of DISC1 in SH-SY5Y cells induces the assembly of eIF3- and TIA-1-positive stress granules (SGs), discrete cytoplasmic granules formed in response to environmental stresses. Our findings suggest that DISC1 may function as a translational regulator and may be involved in stress response.
- Published
- 2005
- Full Text
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13. The mammalian homolog of the Drosophila discs large tumor suppressor protein up-regulates expression of the ELR+ CXC chemokine Scyb5.
- Author
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Aiba T, Kohu K, Ishidao T, Yasui N, Horii A, Aburatani H, and Akiyama T
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Cells, Cultured, Chemokine CXCL5, Chemokines, CXC genetics, Discs Large Homolog 1 Protein, Gene Expression Profiling, Guanylate Kinases, Humans, Membrane Proteins, Mice, Up-Regulation, Chemokines, CXC biosynthesis, Proteins metabolism, Tumor Suppressor Proteins metabolism
- Abstract
The mammalian homolog of the Drosophila discs large tumor suppressor protein Dlg functions as a scaffolding protein that facilitates the transmission of diverse signals. In the present study, we attempted to identify the downstream target genes of Dlg, and found that Dlg up-regulates expression of the ELR+ CXC chemokine Scyb5, which has been implicated in the immune system. Our finding suggests that Scyb5 may play an important role in the tumor suppressor function of Dlg.
- Published
- 2005
- Full Text
- View/download PDF
14. Transcriptional regulation of the TGF-beta pseudoreceptor BAMBI by TGF-beta signaling.
- Author
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Sekiya T, Oda T, Matsuura K, and Akiyama T
- Subjects
- Cell Line, Tumor, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Genes, Regulator genetics, Hepatoblastoma genetics, Humans, Liver Neoplasms genetics, Liver Neoplasms metabolism, Membrane Proteins genetics, Nerve Growth Factors, Promoter Regions, Genetic, Receptors, Transforming Growth Factor beta genetics, Receptors, Transforming Growth Factor beta metabolism, Smad Proteins, Smad3 Protein, Smad4 Protein, Trans-Activators genetics, Trans-Activators metabolism, Transforming Growth Factor beta genetics, Hepatoblastoma metabolism, Membrane Proteins metabolism, Signal Transduction, Transcriptional Activation, Transforming Growth Factor beta metabolism, Xenopus Proteins
- Abstract
BAMBI is a transmembrane glycoprotein related to the transforming growth factor-beta (TGF-beta)-family type I receptors and functions as a negative regulator of TGF-beta signaling during development. BAMBI is induced by BMP signaling through the evolutionary conserved BMP-responsive elements in its promoter. Furthermore, we have recently shown that Wnt/beta-catenin signaling activates transcription of BAMBI and that BAMBI expression is aberrantly elevated in most colorectal carcinomas. Here, we show that BAMBI is also directly induced by TGF-beta signaling, through the three tandem repeats of 13 bp sequences containing the SMAD-binding elements, which are distinct from the BMP-responsive element. Our findings suggest that BAMBI transcription is regulated by TGF-beta signaling through direct binding of SMAD3 and SMAD4 to the BAMBI promoter.
- Published
- 2004
- Full Text
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15. USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney.
- Author
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Yanagita M, Oka M, Watabe T, Iguchi H, Niida A, Takahashi S, Akiyama T, Miyazono K, Yanagisawa M, and Sakurai T
- Subjects
- Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Bone Morphogenetic Proteins chemistry, Bone Morphogenetic Proteins metabolism, Cell Line, Embryo, Mammalian anatomy & histology, Embryo, Mammalian metabolism, Embryo, Nonmammalian, Embryonic and Fetal Development, Fetus chemistry, Humans, In Situ Hybridization, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Proteins chemistry, Proteins metabolism, Proto-Oncogene Proteins antagonists & inhibitors, RNA, Messenger analysis, Rats, Sequence Alignment, Tissue Distribution, Wnt Proteins, Xenopus, Bone Morphogenetic Proteins antagonists & inhibitors, Kidney metabolism, Proteins physiology, Zebrafish Proteins
- Abstract
Bone morphogenetic proteins (BMPs) play critical roles in cellular proliferation, differentiation, and programmed cell death in multiple tissues. An increasing body of recent evidence has suggested that classes of molecules collectively termed BMP antagonists play important roles for the local regulation of BMP actions by binding BMPs and neutralizing their activities. Uterine sensitization-associated gene-1 (USAG-1) was previously reported as a gene of unknown function, preferentially expressed in sensitized endometrium of the rat uterus. Here, we show that USAG-1 is abundantly expressed in the kidney and functions as a BMP antagonist. Recombinant USAG-1 binds directly to BMPs and antagonizes the BMP-mediated induction of alkaline phosphatase in C2C12 cells. USAG-1 also induces formation of secondary axis and/or hyperdorsalization when its mRNA is injected to Xenopus embryos. In the early stage of mouse embryogenesis, USAG-1 is expressed in the first and second branchial arches and in metanephros, while in later stages the expression is confined to renal tubules and ameloblasts of teeth. Postnatally, the expression is further restricted to distal tubules of kidney, in a pattern similar to the localization of BMP-7, which has been shown to be important in the development of kidney and preservation of adult renal functions under pathological stresses. Collectively, we suggest that USAG-1 is a BMP antagonist that interacts with BMP-7 in the developing and adult kidney.
- Published
- 2004
- Full Text
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16. Activation of beta-catenin-TCF-mediated transcription by non-receptor tyrosine kinase v-Src.
- Author
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Haraguchi K, Nishida A, Ishidate T, and Akiyama T
- Subjects
- Animals, Cell Line, Cell Line, Tumor, Colorectal Neoplasms etiology, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Dogs, Genes, APC, Humans, MAP Kinase Signaling System, Mutation, Proto-Oncogene Proteins metabolism, Receptor, ErbB-2 metabolism, Transcription Factors genetics, Wnt Proteins, beta Catenin, Cytoskeletal Proteins metabolism, Oncogene Protein pp60(v-src) metabolism, Trans-Activators metabolism, Transcription Factors metabolism, Transcriptional Activation, Zebrafish Proteins
- Abstract
Activation of Wnt signaling is an early event in colorectal tumorigenesis, while aberrant activation of non-receptor tyrosine kinase c-Src occurs during tumor progression. Here, we show that v-Src and receptor tyrosine kinase ErbB2 activate beta-catenin-TCF-mediated transcription. The effect of v-Src was abrogated by a dominant-negative mutant of TCF and the tumor suppressor APC. Furthermore, the effect of v-Src was partially abrogated by a dominant-negative mutant of MAP kinase, suggesting that v-Src exerts its effect at least in part via the MAP kinase pathway. Our finding raises the possibility that aberrantly activated c-Src may enhance Wnt signaling and this may contribute to tumor progression.
- Published
- 2004
- Full Text
- View/download PDF
17. Incorporation of DUF/FACT into chromatin enhances the accessibility of nucleosomal DNA.
- Author
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Seo H, Okuhara K, Kurumizaka H, Yamada T, Shibata T, Ohta K, Akiyama T, and Murofushi H
- Subjects
- Animals, Chromatography, Gel, Dose-Response Relationship, Drug, Female, High Mobility Group Proteins genetics, Histones metabolism, Male, Micrococcal Nuclease pharmacology, Ovum metabolism, Protein Binding, Spermatozoa metabolism, Time Factors, Xenopus, Xenopus Proteins genetics, Chromatin metabolism, DNA metabolism, High Mobility Group Proteins metabolism, Nucleosomes metabolism, Xenopus Proteins metabolism
- Abstract
DNA unwinding factor (DUF) was discovered as an essential DNA replication factor in Xenopus egg extracts. DUF consists of an HMG protein and a homolog of Cdc68p/Spt16p, and has the capability of unwinding dsDNA. Here we have examined the interaction of DUF with chromatin. DUF was incorporated into chromatin assembled from sperm heads and from plasmid DNA in egg extracts. It was revealed that the chromatin assembled in egg extracts immunodepleted of DUF is less sensitive to micrococcal nuclease (NNase) digestion than that assembled in control extracts, indicating that chromatin containing DUF has more decompact structure than that without DUF. Also we found that DUF has a high affinity for core histones in vitro. We suggest that the function of DUF may be to make the chromatin structure accessible to replication factors.
- Published
- 2003
- Full Text
- View/download PDF
18. Binding of the human homolog of the Drosophila discs large tumor suppressor protein to the mitochondrial ribosomal protein MRP-S34.
- Author
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Ogawa F, Adachi S, Kohu K, Shige K, and Akiyama T
- Subjects
- Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Discs Large Homolog 1 Protein, Drosophila, Humans, Immunoblotting, Membrane Proteins, Mitochondrial Proteins genetics, Molecular Sequence Data, Precipitin Tests, Protein Binding physiology, Proteins genetics, Ribosomal Proteins genetics, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Drosophila Proteins, Insect Proteins genetics, Mitochondrial Proteins metabolism, Proteins metabolism, Ribosomal Proteins metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism
- Abstract
The human homolog of the Drosophila discs large tumor suppressor protein (hDLG) functions as a scaffolding protein that facilitates the transmission of diverse downstream signals. Here we show that hDLG interacts through its PDZ domains with the carboxy-terminal S/TXV motif of the mitochondrial ribosomal protein S-34 (MRP-S34). Our results suggest that hDLG interacts with MRP-S34 prior to entry of MRP-S34 into the mitochondria and may be involved in the trafficking of MRP-S34.
- Published
- 2003
- Full Text
- View/download PDF
19. Binding of the mammalian homolog of the Drosophila discs large tumor suppressor protein to the ribosome receptor.
- Author
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Kim M, Ogawa H, Kohu K, Ichikawa M, Satoh K, Ishidao T, Nada S, and Akiyama T
- Subjects
- Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Discs Large Homolog 1 Protein, HeLa Cells, Humans, Membrane Proteins, Molecular Sequence Data, Receptors, Amino Acid, Receptors, Cytoplasmic and Nuclear chemistry, Swine, Proteins metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Tumor Suppressor Proteins metabolism
- Abstract
DLG, the mammalian homolog of the Drosophila Discs Large suppressor protein, functions as a scaffolding protein that facilitates the transmission of diverse downstream signals. In the present study, we attempted to identify partner proteins for DLG, and found that DLG interacts through its PDZ domains with the ribosome receptor. The ribosome receptor is an integral endoplasmic reticulum protein that has been suggested to be involved in secretion. Our finding raises the possibility that DLG plays a role in the regulation of secretion by interacting with the ribosome receptor.
- Published
- 2002
- Full Text
- View/download PDF
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