15 results on '"Chaogu Zheng"'
Search Results
2. Mid-infrared metabolic imaging with vibrational probes
- Author
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Xinwen Liu, Lars E. P. Dietrich, Wei Min, H. Ted Stinson, Lixue Shi, Chaogu Zheng, Lingyan Shi, Christopher R. Evans, Jeremy Rowlette, and Lisa Juliane Kahl
- Subjects
In situ ,Technology ,Nonlinear Optical Microscopy ,Spectrophotometry, Infrared ,Mid infrared ,Biochemistry ,Medical and Health Sciences ,Vibration ,Article ,03 medical and health sciences ,Mice ,Neoplasms ,Microscopy ,Animals ,Caenorhabditis elegans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Chemistry ,Extramural ,Metabolic imaging ,Brain ,Cell Biology ,Biological Sciences ,Nonlinear optical microscopy ,High-Throughput Screening Assays ,Spectrophotometry ,Biophysics ,Single-Cell Analysis ,Infrared microscopy ,Infrared ,Biotechnology ,Developmental Biology - Abstract
Understanding metabolism is indispensable to unraveling the mechanistic basis of many physiological and pathological processes. However, in situ metabolic imaging tools are still lacking. Herein we introduce a framework for mid-infrared (MIR) metabolic imaging by coupling the emerging high-information-throughput MIR microscopy with specifically designed IR-active vibrational probes. Three categories of small vibrational tags including azide bond, 13C-edited carbonyl bond and deuterium-labeled probes are presented to interrogate various metabolic activities in cells, small organisms and mice. Two MIR imaging platforms are implemented including broadband Fourier transform infrared (FTIR) microscopy and discrete frequency infrared (DFIR) microscopy with a newly incorporated spectral region (2000–2300 cm−1). Our technique is uniquely suited for metabolic imaging with high-information-throughput. In particular, we performed single-cell metabolic profiling including heterogeneity characterization, and large-area metabolic imaging at tissue/organ level with rich spectral information., Editor’s summary Small vibrational tags (azide, 13C-edited carbonyl, and deuterium-labeled probes) were introduced as metabolic probes for mid-infrared imaging. The tags allow unprecedented in situ visualization of metabolism in cells and animals with high information-throughput.
- Published
- 2020
3. Nervous system-wide analysis of Hox regulation of terminal neuronal fate specification in Caenorhabditis elegans
- Author
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Ho Ming Terence Lee, Chaogu Zheng, and Kenneth Pham
- Subjects
Homeodomain Proteins ,Neurons ,Cancer Research ,animal structures ,embryonic structures ,Genetics ,Genes, Homeobox ,Animals ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics - Abstract
Hox genes encode evolutionarily conserved transcription factors that specify regional identities along the anterior-posterior (A-P) axis. Although some Hox genes are known to regulate the differentiation of certain neurons, to what extent Hox genes are involved in the terminal specification of the entire nervous system is unclear. Here, we systematically mapped the expression of all six Hox genes in C. elegans nervous system and found Hox expression in 97 (32%) of the 302 neurons in adult hermaphrodites. Our results are generally consistent with previous high-throughput expression mapping and single-cell transcriptomic studies. Detailed analysis of the fate markers for these neurons revealed that Hox genes regulate the differentiation of 29 (25%) of the 118 classes of C. elegans neurons. Hox genes not only regulate the specification of terminal neuronal fates through multiple mechanisms but also control subtype diversification along the A-P axis. The widespread involvement of Hox genes in neuronal differentiation indicates their roles in establishing complex nervous systems.
- Published
- 2021
4. Whole-cell FRET monitoring of transcription factor activities enables functional annotation of signal transduction systems in living bacteria
- Author
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Pengchao Wang, Guangming Zhang, Zeling Xu, Zhe Chen, Xiaohong Liu, Chenyin Wang, Chaogu Zheng, Jiangyun Wang, Hongmin Zhang, and Aixin Yan
- Subjects
Host Microbial Interactions ,Escherichia coli ,Fluorescence Resonance Energy Transfer ,Animals ,Cell Biology ,Organic Chemicals ,Single-Cell Analysis ,Caenorhabditis elegans ,Molecular Biology ,Biochemistry ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
Bacteria adapt to their constantly changing environments largely by transcriptional regulation through the activities of various transcription factors (TFs). However, techniques that monitor TF-promoter interactions in situ in living bacteria are lacking. Herein, we developed a whole-cell TF-promoter binding assay based on the intermolecular FRET between an unnatural amino acid, l-(7-hydroxycoumarin-4-yl) ethylglycine, which labels TFs with bright fluorescence through genetic encoding (donor fluorophore) and the live cell nucleic acid stain SYTO 9 (acceptor fluorophore). We show that this new FRET pair monitors the intricate TF-promoter interactions elicited by various types of signal transduction systems, including one-component (CueR) and two-component systems (BasSR and PhoPQ), in bacteria with high specificity and sensitivity. We demonstrate that robust CouA incorporation and FRET occurrence is achieved in all these regulatory systems based on either the crystal structures of TFs or their simulated structures, if 3D structures of the TFs were unavailable. Furthermore, using CueR and PhoPQ systems as models, we demonstrate that the whole-cell FRET assay is applicable for the identification and validation of complex regulatory circuit and novel modulators of regulatory systems of interest. Finally, we show that the FRET system is applicable for single-cell analysis and monitoring TF activities in Escherichia coli colonizing a Caenorhabditis elegans host. In conclusion, we established a tractable and sensitive TF-promoter binding assay, which not only complements currently available approaches for DNA-protein interactions but also provides novel opportunities for functional annotation of bacterial signal transduction systems and studies of the bacteria-host interface.
- Published
- 2022
5. Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans
- Author
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Ho Ming Terence Lee, Chaogu Zheng, David H. Hall, Martin Chalfie, Ken C. Q. Nguyen, Emily Atlas, and Susan Laura Javier Jao
- Subjects
0303 health sciences ,biology ,Cellular differentiation ,biology.organism_classification ,F-box protein ,Hsp90 ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,Microtubule ,Chaperone (protein) ,biology.protein ,Protein folding ,Molecular Biology ,030217 neurology & neurosurgery ,Caenorhabditis elegans ,030304 developmental biology ,Developmental Biology ,Microtubule nucleation - Abstract
Molecular chaperones often work collaboratively with the ubiquitination-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of Caenorhabditis elegans, we find that mec-15(-) mutants display defects in microtubule formation, neurite growth, synaptic development, and neuronal functions, and these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and cochaperones. MEC-15 likely functions in a SCF complex to degrade DLK-1, which is an Hsp90 client protein stabilized by the chaperones. The abundance of DLK-1, and likely other Hsp90 substrates, is fine-tuned by the antagonism between MEC-15 and chaperones; this antagonism regulates TRN development as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between UPS and chaperones tightly controls neuronal differentiation.
- Published
- 2020
6. TBA-7 is not a microtubule-destabilizing tubulin
- Author
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Yu-Ming Lu and Chaogu Zheng
- Subjects
Tubulin ,biology ,Microtubule ,Biophysics ,biology.protein ,Animals ,Humans ,Cell Biology ,Molecular Biology ,Letter to the Editor ,Microtubules - Published
- 2021
7. Distinct effects of tubulin isotype mutations on neurite growth inCaenorhabditis elegans
- Author
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David H. Hall, Chaogu Zheng, Margarete Diaz-Cuadros, Ken C. Q. Nguyen, and Martin Chalfie
- Subjects
0301 basic medicine ,macromolecular substances ,Cell Biology ,Biology ,biology.organism_classification ,Isotype ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Neurite growth ,Tubulin ,Microtubule ,biology.protein ,Missense mutation ,Molecular Biology ,Gene ,Caenorhabditis elegans - Abstract
Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization.
- Published
- 2017
8. Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons ofCaenorhabditis elegans
- Author
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Ji Wu, Chaogu Zheng, Brian L. Trippe, Felix Qiaochu Jin, and Martin Chalfie
- Subjects
0301 basic medicine ,0303 health sciences ,animal structures ,biology ,Effector ,fungi ,Regulator ,Repressor ,Cell fate determination ,biology.organism_classification ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Negative feedback ,embryonic structures ,Touch receptor ,Nociceptor ,Molecular Biology ,Gene ,Transcription factor ,030217 neurology & neurosurgery ,Caenorhabditis elegans ,Developmental Biology ,030304 developmental biology - Abstract
Terminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called “terminal selectors” that directly activate a set of downstream effector genes. InCaenorhabditis elegansthe differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons utilize the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. Since EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative feedback loop that regulates the choice between the two neuronal fates.Summary statement:Transcriptional repressors regulate binary fate choices through reciprocal inhibition during terminal neuronal differentiation. Specifically, ZEB family transcription factor safeguards fate specification of touch receptor neuron by inhibiting TEA domain-containing repressor.
- Published
- 2018
9. Distinct effects of tubulin isotype mutations on neurite growth inCaenorhabditis elegans
- Author
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Martin Chalfie, Margarete Diaz-Cuadros, David H. Hall, Susan Laura Jao, Ken C. Q. Nguyen, and Chaogu Zheng
- Subjects
0303 health sciences ,biology ,Neurite ,macromolecular substances ,biology.organism_classification ,Isotype ,Molecular biology ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,Tubulin ,Microtubule ,biology.protein ,Missense mutation ,Binding site ,Gene ,030217 neurology & neurosurgery ,Caenorhabditis elegans ,030304 developmental biology - Abstract
Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using theC. eleganstouch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations intoC. elegansgenes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization.Table of Content (TOC) Highlight SummaryDifferent tubulin isotypes perform different functions in the regulation of MT structure and neurite growth, and missense mutations of tubulin genes have three types of distinct effects on MT stability and neurite growth. One α-tubulin isotype appears to induce relative instability due to the lack of potential post-translational modification sites.
- Published
- 2017
10. Targeted Knockdown of EGR-1 Inhibits IL-8 Production and IL-8-mediated Invasion of Prostate Cancer Cells through Suppressing EGR-1/NF-κB Synergy
- Author
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Yinghui Fang, Baolin Sun, Jiajia Ma, Weihua Xiao, Yang Ma, Ting Xue, Lu Xu, Ying Zhao, Chaogu Zheng, and Zijia Ren
- Subjects
Male ,Biology ,Biochemistry ,Metastasis ,Prostate cancer ,DU145 ,Cell Line, Tumor ,Genetic model ,Gene Knockdown Techniques ,medicine ,Animals ,Humans ,Gene silencing ,Neoplasm Invasiveness ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Early Growth Response Protein 1 ,Gene knockdown ,Interleukin-8 ,Mechanisms of Signal Transduction ,NF-kappa B ,Prostatic Neoplasms ,Genetic Therapy ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,body regions ,Cancer research ,hormones, hormone substitutes, and hormone antagonists - Abstract
IL-8 produced by prostate cancer cells may be responsible for the androgen-independent growth of advanced prostate cancers. Accumulating evidence from microarray analyses and animal genetic models highlights the central involvement of the transcription factor early growth response-1 (EGR-1) in prostate carcinoma progression. It is unknown, however, whether knockdown of EGR-1 inhibits IL-8 production and IL-8-mediated tumor metastasis. Here we show that EGR-1 knockdown by a specific shRNA-Egr1 inhibited gene transcription and production of IL-8 by the human prostate cancer cell line DU145. Conversely, enforced expression of EGR-1 in EGR-1-lacking PC3 prostate cancer cells markedly enhanced IL-8 transcription and secretion. By using wild type and a series of mutant IL-8 promoter luciferase constructs, we found that the NF-kappaB binding site is important for EGR-1 regulation of IL-8. Furthermore, silencing EGR-1 suppressed a synergistically functional interaction between EGR-1 and NF-kappaB. Consequently, knockdown of EGR-1 inhibited IL-8-mediated tumor colony formation and invasion. Thus, targeted knockdown of EGR-1 could be an effective therapeutic approach against prostate cancer.
- Published
- 2009
11. Low concentration of condensed tannins from catechu significantly inhibits fatty acid synthase and growth of MCF-7 cells
- Author
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Wei Xi Tian, Chaogu Zheng, Shu Yan Zhang, and Xiyun Yan
- Subjects
chemistry.chemical_classification ,biology ,Astringent ,Chemistry ,Biophysics ,Cell Biology ,Catechu ,Biochemistry ,Fatty Acid Synthase, Type I ,Inhibitory Concentration 50 ,Fatty acid synthase ,Proanthocyanidin ,MCF-7 ,Cell Line, Tumor ,biology.protein ,Chemical Precipitation ,Humans ,Condensed tannin ,Enzyme Inhibitors ,Tannins ,Molecular Biology ,IC50 ,Areca ,Volume concentration - Abstract
Tannins exist widely in plants, but because they precipitate proteins, scientists frequently ignore them in search of bioactive components. Catechu, a traditional astringent, is rich in tannins. In this study, we found that condensed tannins from catechu potently inhibited animal fatty acid synthase (FAS). Among them, trimeric condensed tannin showed the most potent inhibition with IC(50) of 0.47 microg/ml and it also exhibited strong time-dependent inhibition. Its inhibitory kinetics and reacting sites on FAS were obviously different from the known inhibitors of FAS. Furthermore, condensed tannins were found to suppress the growth of MCF-7 breast cancer cells, and the effect was related to their activity of FAS inhibition. The inhibition of both FAS activity and MCF-7 growth was exhibited by low concentrations of condensed tannins without FAS being precipitated. These results suggest tannins would be a valuable resource of bioactive substances.
- Published
- 2008
12. Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration
- Author
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Xiyun Yan, Jie Zhuang, Yongting Luo, Shu Xing, Chaogu Zheng, Jinbin Zhang, Jing Feng, Dongling Yang, and Di Lu
- Subjects
Phosphatidylinositol 4,5-Diphosphate ,Cancer Research ,RHOA ,Skin Neoplasms ,Cell ,Motility ,CD146 Antigen ,Biology ,Cell Movement ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,rho-Specific Guanine Nucleotide Dissociation Inhibitors ,Phosphorylation ,Molecular Biology ,Melanoma ,Guanine Nucleotide Dissociation Inhibitors ,rho-Associated Kinases ,Microvilli ,Cell migration ,medicine.disease ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Cell culture ,Cancer research ,biology.protein ,CD146 ,rhoA GTP-Binding Protein ,Transcription Factors - Abstract
Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.
- Published
- 2011
13. Generation and characterization of a panel of monoclonal antibodies against distinct epitopes of human CD146
- Author
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Dongling Yang, Chaogu Zheng, Jing Feng, Jinbin Zhang, Ying Zhang, Di Lu, and Xiyun Yan
- Subjects
medicine.drug_class ,Immunology ,Antibodies, Monoclonal ,Endothelial Cells ,CD146 Antigen ,Biology ,Monoclonal antibody ,Molecular biology ,Transmembrane protein ,Epitope ,Blot ,Mice ,Epitope mapping ,medicine ,biology.protein ,Immunology and Allergy ,Immunohistochemistry ,CD146 ,Animals ,Humans ,Endothelium, Vascular ,Antibody ,Cells, Cultured ,Epitope Mapping - Abstract
CD146 (MUC18, Mel-CAM/MCAM) is a transmembrane protein, originally identified as a biomarker of melanoma, and plays an important role in cancer invasion and metastasis. Further studies revealed that CD146 as a novel endothelial marker was also involved in angiogenesis. Previous studies reported several anti-CD146 antibodies, such as MUC18, A32, S-endo1, and P1H12, showing different binding patterns to the endothelium of various types of blood vessels. To examine the possibility that antibodies targeting different epitopes on CD146 could have different behaviors, we generated a panel of anti-human CD146 monoclonal antibodies, named AA1-5 and AA7, by immunizing mice with human CD146 protein purified from HUVEC. Their specificity and binding affinity were intensively characterized using Western blotting, flow cytometry, and immunohistochemical assay. On the basis of epitope mapping, we divided the six monoclonal antibodies (MAb) into two groups, groups V1 and C2-2, corresponding to the different extracellular domains harboring these epitopes, the first IgV and the second IgC2 domains, respectively. Furthermore, owing to different epitopes, the two groups of antibodies behaved differentially in cellular and histological levels. Therefore, these anti-CD146 MAbs targeting different domains should be useful tools in studying the expression and function of human CD146.
- Published
- 2008
14. Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
- Author
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Siavash Karimzadegan, Martin Chalfie, Chaogu Zheng, and Victor Chiang
- Subjects
Cancer Research ,Epigenetic regulation of neurogenesis ,lcsh:QH426-470 ,Cellular differentiation ,Methylation ,Epigenesis, Genetic ,Vulva ,Histones ,03 medical and health sciences ,DNA-binding proteins ,Histone methylation ,Genetics ,Animals ,Epigenetics ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Homeodomain Proteins ,Neurons ,Regulation of gene expression ,0303 health sciences ,biology ,fungi ,030302 biochemistry & molecular biology ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Cell Differentiation ,Molecular biology ,Cell biology ,lcsh:Genetics ,Histone ,nervous system ,FOS: Biological sciences ,Epigenetic Repression ,Histone methyltransferase ,biology.protein ,Female ,Gene expression ,Signal Transduction ,Research Article - Abstract
Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor gene unc-4, require histone modification, most likely H3K9 methylation. An EGF signal from the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription factor LIN-11 and histone demethylases removed the suppressive histone marks and derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help establish subtype-specific gene expression, which are needed for optimal activity of a neural circuit., Author Summary As neurons differentiate they express specific genes that give them their distinctive shapes, activities, and functions. Much of this differentiation is controlled by the expression of transcription factors, proteins that turn on the expression of other genes. We find, however, that another aspect of terminal neuronal differentiation is the removal of inhibitory constraints on gene expression. These constraints often involve the modification of DNA or of general DNA binding proteins such as histones. This modification, referred to as epigenetic regulation, can activate or inactive genes without changing the genetic material. We found that the differentiation of nematode motor neurons was affected by genes involved in histone modification. Specifically, a gene that is needed in a subset of the motor neurons is initially turned off in all cells by histone modification. Mutation of histone modification genes causes the gene to be on in all cells. Normally, however, this removal of the inhibition is triggered by an external signal that only affects the specific cells.
- Published
- 2013
15. A Novel Anti-CEACAM5 Monoclonal Antibody, CC4, Suppresses Colorectal Tumor Growth and Enhances NK Cells-Mediated Tumor Immunity
- Author
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Ping Wang, Xiyun Yan, Jing Feng, Dongling Yang, Di Lu, Chaogu Zheng, Shu Xing, and Jean-Luc Coll
- Subjects
Colorectal cancer ,medicine.drug_class ,Science ,Molecular Sequence Data ,Immunology ,Cancer Treatment ,Tumor M2-PK ,NK cells ,Gastroenterology and Hepatology ,Monoclonal antibody ,Mice ,Carcinoembryonic antigen ,Antibody Therapy ,Antibody Specificity ,Cell Movement ,Gastrointestinal Cancers ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Antigens ,Biology ,Cell Aggregation ,Cell Proliferation ,Antibody-dependent cell-mediated cytotoxicity ,Immunity, Cellular ,Multidisciplinary ,biology ,Immune cells ,Antibody-Dependent Cell Cytotoxicity ,Antibodies, Monoclonal ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular biology ,Cell aggregation ,Carcinoembryonic Antigen ,Killer Cells, Natural ,Oncology ,biology.protein ,Medicine ,Antibody ,Colorectal Neoplasms ,Epitope Mapping ,Research Article - Abstract
Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic.
- Published
- 2011
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