المؤلفون: Bing Cui, Chen-xi Zhao, Bo Huang, Jiao-jiao Yu, Xiaoxi Lv, Xiaowei Zhang, Ke Li, Xia Li, Zhuo-Wei Hu, Tingting Zhang, Fang Hua, Zhao-na Yang, Feng Wang

المصدر: Oncogene. 37:2967-2981

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Down-Regulation, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biology, Lysine Acetyltransferase 5, Metastasis, Mice, 03 medical and health sciences, Downregulation and upregulation, Cell Movement, Cell Line, Tumor, Genetics, medicine, Animals, Humans, Smad3 Protein, KAT5, Melanoma, Molecular Biology, Cell Proliferation, Regulation of gene expression, Autophagy, Acetylation, medicine.disease, Xenograft Model Antitumor Assays, Metformin, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Repressor Proteins, 030104 developmental biology, TRIB3, Disease Progression, Cancer research, medicine.drug

الوصف: Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression. Thus, TRIB3 is a potential therapeutic target for diverse cancers. In this study, we found that metformin attenuates melanoma growth and metastasis by reducing TRIB3 expression in non-diabetic C57BL/6 mice and diabetic KK-Ay mice; overexpression of TRIB3 protects metformin from the activation of autophagic flux, the clearance of accumulated tumour-promoting factors and the attenuation of tumour progression. We further elucidated that TRIB3 acts as an adaptor to recruit lysine acetyltransferase 5 (KAT5) to SMAD3 and induce a phosphorylation-dependent K333 acetylation of SMAD3, which sustains transcriptional activity of SMAD3 and subsequently enhances TRIB3 transcription. Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression. Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdf3fc36f148445cdb5fc4df10ec00d2Test
https://doi.org/10.1038/s41388-018-0172-9Test

المؤلفون: Bing Cui, Fang Hua, Cai-Cai Jin, Chen-xi Zhao, Jin-mei Yu, Bo Huang, Ke Li, Shan-Shan Liu, Xue-ying Hou, Xiaoxi Lv, Xiaowei Zhang, Ji-Chao Zhou, Zhuo-Wei Hu, Dian Peng, Jiao-jiao Yu, Feng Wang, Zhao-na Yang

المصدر: Autophagy

مصطلحات موضوعية: 0301 basic medicine, Liver Cirrhosis, Cell Cycle Proteins, Mice, Transgenic, Biology, Protein Serine-Threonine Kinases, Exosome, 03 medical and health sciences, Sequestosome 1, Fibrosis, Sequestosome-1 Protein, medicine, Autophagy, Animals, Humans, education, Molecular Biology, education.field_of_study, 030102 biochemistry & molecular biology, Cell Biology, BECN1, medicine.disease, Cell biology, Repressor Proteins, 030104 developmental biology, TRIB3, Hepatic stellate cell, Hepatocytes, Hepatic fibrosis, Research Paper

الوصف: Impaired macroautophagy/autophagy is involved in the pathogenesis of hepatic fibrosis. However, how aberrant autophagy promotes fibrosis is far from understood. Here, we aimed to define a previously unrevealed pro-fibrotic mechanism for the stress protein TRIB3 (tribbles pseudokinase 3)-mediated autophagy dysfunction. Human fibrotic liver tissues were obtained from patients with cirrhosis who underwent an open surgical repair process. The functional implications of TRIB3 were evaluated in mouse models of hepatic fibrosis induced by bile duct ligation (BDL) or thioacetamide (TAA) injection. Human fibrotic liver tissues expressed higher levels of TRIB3 and selective autophagic receptor SQSTM1/p62 (sequestosome 1) than nonfibrotic tissues and the elevated expression of TRIB3 and SQSTM1 was positively correlated in the fibrotic tissues. Silencing Trib3 protected against experimentally induced hepatic fibrosis, accompanied by restored autophagy activity in fibrotic liver tissues. Furthermore, TRIB3 interacted with SQSTM1 and hindered its binding to MAP1LC3/LC3, which caused the accumulation of SQSTM1 aggregates and obstructed autophagic flux. The TRIB3-mediated autophagy impairment not only suppressed autophagic degradation of late endosomes but also promoted hepatocellular secretion of INHBA/Activin A-enriched exosomes which caused migration, proliferation and activation of hepatic stellate cells (HSCs), the effector cells of liver fibrosis. Disrupting the TRIB3-SQSTM1 interaction with a specific helical peptide exerted potent protective effects against hepatic fibrosis by restoring autophagic flux in hepatocytes and HSCs. Together, stress-elevated TRIB3 expression promotes hepatic fibrosis by interacting with SQSTM1 and interfering with its functions in liver-parenchymal cells and activating HSCs. Targeting this interaction is a promising strategy for treating fibroproliferative liver diseases. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTA2/α-SMA: actin, alpha 2, smooth muscle, aorta; BDL: bile duct ligation; BECN1/Beclin 1: beclin 1, autophagy related; CHX: cycloheximide; CQ: chloroquine; Edu: 5-ethynyl-2-deoxyuridine; ESCRT: endosomal sorting complexes required for transport; HSC: hepatic stellate cell; ILV: intralumenal vesicle; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MVB: multivesicular body; PIK3C3: phosphatidylinositol 3-kinase, catalytic subunit type 3; PPI: protein-protein interaction; SQSTM1/p62: sequestosome 1; TAA: thioacetamide; TEM: transmission electron microscopy; TGFB1/TGFβ1: transforming growth factor, beta 1; TLR2: toll-like receptor 2; TRIB3: tribbles pseudokinase 3

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41a64689ef90bcc9dd1da00673810dbfTest

المؤلفون: Zhuo-Wei Hu, Fang Hua, Ting-ting Zhang, Ke Li

المصدر: Autophagy. 14:1278-1279

مصطلحات موضوعية: 0301 basic medicine, Antineoplastic Agents, Biology, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Autophagy, medicine, Animals, Smad3 Protein, Epigenetics, KAT5, Melanoma, Molecular Biology, Lysine Acetyltransferase 5, Cell Biology, Metformin, Mice, Inbred C57BL, Repressor Proteins, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Disease Progression, Commentary, Cancer research, Phosphorylation, Flux (metabolism), medicine.drug

الوصف: Deregulation of metabolism during melanoma progression is tightly associated with the genetic and epigenetic alterations of metabolic regulators. Metformin, a macroautophagy/autophagy inducer, has beneficial effects of preventing and treating multiple cancers with an unclear mechanism. Enhanced pseudokinase TRIB3 was reported to link metabolic stressors to melanoma promotion by inhibiting autophagy and ubiquitin-proteasome degradation systems. Here, we discuss our recent findings regarding how metformin reduces TRIB3 expression to restore autophagic flux and suppress melanoma progression in non-diabetic and diabetic mice. We found that overexpression of TRIB3 reverses the metformin-activated autophagic flux, clearance of accumulated tumor-promoting factors and inhibition of tumor progression. Mechanistically, TRIB3 interacts with KAT5 (lysine acetyltransferase 5) and promotes the physical association of KAT5 and SMAD3, which enhances SMAD3 K333 acetylation in a phosphorylation-dependent manner, sustains SMAD3 transcriptional activity and induces TRIB3 expression. Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression. Our finding defines a molecular mechanism by which metformin targets TRIB3 expression to induce autophagy and protect against melanoma progression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b76d5a78872247f23f8b2ebae0a73a2fTest
https://doi.org/10.1080/15548627.2018.1460022Test

المؤلفون: Xiangliang Yang, Jinzhi Lu, Yong Li, Xuetao Cao, Huafeng Zhang, Xiuli Luo, Bo Huang, Shunqun Luo, Chengyin Li, Ke Tang, Yi Zhang, Jingwei Ma, Tianzhen Zhang, Hongwei Gong, Yang Jin, Shuang Zhang, Ruihua Ma, Junwei Chen, Tiantian Ji, Yanling Sun, Xiaonan Yin, Pingwei Xu, Zhixiong Long, Ning Wang, Zhuo-Wei Hu

المصدر: Cell research. 26(6)

مصطلحات موضوعية: 0301 basic medicine, Drug, media_common.quotation_subject, Antineoplastic Agents, Soft Tissue Neoplasms, Drug resistance, Pharmacology, Biology, Microtubules, Cell-Derived Microparticles, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Cell Line, Tumor, medicine, Animals, Humans, Doxorubicin, Molecular Biology, media_common, Cell Nucleus, Mice, Inbred BALB C, technology, industry, and agriculture, Cancer, Cell Biology, medicine.disease, Survival Analysis, Research Highlight, Pleural Effusion, 030104 developmental biology, Cell culture, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer cell, Neoplastic Stem Cells, Efflux, medicine.drug

الوصف: Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce217524896c761e6d5e8fd2f0138cacTest
https://pubmed.ncbi.nlm.nih.gov/27167570Test

المؤلفون: Ke Li, Fang Hua, Zhuo-Wei Hu, Jiao-jiao Yu

المصدر: Autophagy. 11(10)

مصطلحات موضوعية: Carcinogenesis, Autophagy, Cancer, Cell Biology, Biology, medicine.disease_cause, medicine.disease, Ubiquitinated Proteins, Autophagic Puncta, IRS1, Metastasis, Cell biology, Cell Transformation, Neoplastic, Stress, Physiological, Neoplasms, medicine, Gene silencing, Animals, Humans, Receptor, Molecular Biology, Flux (metabolism)

الوصف: Cancer and diabetes are 2 multifactorial chronic diseases with tremendous impact on health worldwide. Metabolic risk factors play a critical role in fueling a wide range of cancers, but with undefined mechanisms. We recently reported that TRIB3, a stress-induced protein, mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin-IGF1 to malignant promotion. We found that several human cancer tissues express higher TRIB3 and phosphorylated IRS1 (insulin receptor substrate 1), which correlates negatively with patient prognosis. Silencing of TRIB3 not only restores insulin-IGF1-suppressed autophagic flux, but also attenuates tumor growth and metastasis. TRIB3 physically interacts with the autophagic receptor SQSTM1, and this interaction hinders the binding of SQSTM1 to LC3 and ubiquitinated proteins, leading to SQSTM1 accumulation and clearance inhibition of ubiquitinated proteins. Interrupting the TRIB3-SQSTM1 interaction with an α-helical peptide derived from SQSTM1 attenuates tumor growth and metastasis through activating autophagic flux. Our findings indicate that TRIB3 links insulin-IGF1 to cancer development and progression through interacting with SQSTM1. Thus, interrupting the TRIB3-SQSTM1 interaction may provide a potential strategy against cancers in patients with diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5cfd603f34e0e75e0e4dd4b6423210ceTest
https://pubmed.ncbi.nlm.nih.gov/26301314Test

المؤلفون: Qingqing Wang, Zhuo-Wei Hu, Huimin Yan, Xiao-xing Wang, Yonggang Ma, Xiaowei Zhang, Su Mi, Hong-Zhen Yang, Han-zhi Liu

المصدر: Acta Pharmacologica Sinica. 32:1045-1054

مصطلحات موضوعية: Pathology, medicine.medical_specialty, medicine.medical_treatment, Flow cytometry, Pathogenesis, Mice, Western blot, medicine, Animals, Pharmacology (medical), Receptor, Pharmacology, Mice, Inbred C3H, medicine.diagnostic_test, business.industry, Interleukin-17, General Medicine, Molecular biology, Toll-Like Receptor 4, Cytokine, Bronchoalveolar lavage, Pulmonary Emphysema, Apoptosis, Mutation, Th17 Cells, Original Article, Interleukin 17, business

الوصف: To explore the pathogenic role of Th17 cells and interleukin-17A (IL-17A)-associated signaling pathways in spontaneous pulmonary emphysema induced by a Toll-like receptor 4 mutant (TLR4(mut)).Lungs were obtained from wild-type (WT) or TLR4mut mice that were treated with or without recombinant mouse IL-17A (1 μg·kg(-1)·d(-1), ip) from the age of 3 weeks to 3 months. Pulmonary emphysema was determined using histology, immunochemistry, and biochemical analysis. T cell polarization was determined with flow cytometry, the levels of cytokines were measured using ELISA, and the levels of IL-17A-associated signaling molecules were detected using Western blot.Compared to WT mice, 3 month-old TLR4(mut) mice were characterized by significantly reduced infiltration of Th17 cells into lungs (2.49%±1.13 % νs 5.26%±1.39%), and significantly reduced expression levels of IL-17A (3.66±0.99 pg/μg νs 10.67±1.65 pg/μg), IL-23 (12.43±1.28 pg/μg νs 28.71±2.57 pg/μg) and IL-6 (51.82±5.45 pg/μg νs 92.73±10.91 pg/μg) in bronchoalveolar lavage fluid. In addition, p38 MAPK phosphorylation and AP-1 expression were decreased to 27%±9% and 51%±8%, respectively, of that in WT mice. Treatment of TLR4(mut) mice with IL-17A increased the infiltration of Th17 cells into lungs and expression levels of IL-17A, IL-6, and IL-23 in bronchoalveolar lavage fluid, attenuated MDA and apoptosis, and improved emphysema accompanied with increased phosphorylation of p38 MAPK and expression of AP-1.Th17 cells, in particular the cytokine IL-17A, play a crucial role in the pathogenesis of TLR4(mut)-induced spontaneous pulmonary emphysema. Both of them are potential targets for therapeutic strategies for pulmonary emphysema.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68c6ed7198d21a72fe6d8b6783f07cfeTest
https://doi.org/10.1038/aps.2011.67Test

المؤلفون: Xiao-You Shi, Zhuo-Wei Hu, Brian B. Hoffman, Richard Z. Lin

المصدر: Molecular Endocrinology. 13:3-14

مصطلحات موضوعية: GTPase-activating protein, G protein, Biology, Transfection, Proto-Oncogene Proteins p21(ras), Mice, Norepinephrine, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Endocrinology, GTP-binding protein regulators, GTP-Binding Proteins, Receptors, Adrenergic, alpha-1, Animals, Humans, Virulence Factors, Bordetella, Phosphatidylinositol, Protein kinase A, Molecular Biology, G protein-coupled receptor kinase, Kinase, 3T3 Cells, General Medicine, Cyclic AMP-Dependent Protein Kinases, Molecular biology, Recombinant Proteins, Cell biology, Enzyme Activation, Pertussis Toxin, chemistry, beta-Adrenergic Receptor Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Mutation, Signal transduction, Adrenergic alpha-Agonists, Signal Transduction

الوصف: Activation of protein kinases is an important intermediate step in signaling pathways of many G protein-coupled receptors including alpha1-adrenergic receptors. The present study was designed to investigate the capacity of the three cloned subtypes of human alpha1-receptors, namely, alpha1A, alpha1B and alpha1D to activate phosphatidylinositol 3-kinase (PI 3-kinase) and p21ras in transfected NIH3T3 cells. Norepinephrine activated PI 3-kinase in cells expressing human alpha1A and alpha1B via pertussis toxin-insensitive G proteins; alpha1D-receptors did not detectably activate this kinase. Transient transfection of NIH 3T3 cells with the alpha-subunit of the G protein transducin (alpha(t)) a scavenger of betagamma-subunits released from activated G proteins, inhibited alpha1B-receptor but not alpha1A-receptor-stimulated PI 3-kinase activity. Stimulation of both alpha1A- and alpha1B-receptors activated p21ras and stimulated guanine nucleotide exchange on Ras protein. Overexpression of a dominant negative mutant of p21ras attenuated alpha1B-receptor but not alpha1A-receptor activation of PI 3-kinase. Overexpression of a dominant negative mutant of PI 3-kinase attenuated alpha1A- but not alpha1B-receptor-stimulated mitogen-activated protein kinase activity. These results demonstrate the capacity for heterologous signaling of the alpha1-adrenergic receptor subtypes in promoting cellular responses in NIH3T3 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8ecffa667de67a9e0b91406b02283d7Test
https://doi.org/10.1210/mend.13.1.0215Test

المؤلفون: Fang Hua, Zhuo-Wei Hu, Heng Lin, Ziyan Wang

المصدر: Autophagy. 9(6)

مصطلحات موضوعية: Senescence, Ku80, Carcinoma, Hepatocellular, DNA Repair, DNA repair, DNA damage, Carcinogenesis, Biology, medicine.disease_cause, Models, Biological, medicine, Autophagy, Animals, Humans, Molecular Biology, Ku Autoantigen, Cellular Senescence, Ku70, Liver Neoplasms, Antigens, Nuclear, Cell Biology, digestive system diseases, Autophagic Punctum, Non-homologous end joining, DNA-Binding Proteins, Toll-Like Receptor 4, Cancer research, Reactive Oxygen Species, Cell aging, DNA Damage

الوصف: Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. The initiation and progression of HCC is closely associated with chronic liver inflammation. Recent research indicates that nonhomologous end joining (NHEJ), one of the DNA repair mechanisms, autophagy and senescence are all involved in the pathogenesis of HCC induced by carcinogens or oxidative stress. DNA repair proteins including XRCC6/KU70 and XRCC5/KU80 are the critical NHEJ factors that play pivotal roles in genome-maintenance issues such as DNA replication and repair, telomere maintenance and chromosomal instability. Our studies indicate that a deficiency of toll-like receptor 4 (TLR4)-mediated immune activities results in a decreased expression of XRCC5 and XRCC6 in response to insult by the carcinogen diethylnitrosamine (DEN). This effect causes a failure in DNA repair, and promotes the transformation of precancerous hepatocytes and HCC development. Ectopic expression of XRCC6 protects against HCC initiation and progression by restoring the cellular senescent response and activation of immune networks, which induces an effective autophagic degradation, removes the accumulated reactive oxygen species (ROS), decreases DNA damage, attenuates proliferation, and promotes programmed cell death in TLR4-deficient livers. Our work indicates that repairing DNA damage by XRCC6 reverses TLR4-deficiency-worsened HCC development via restoring immunity to support senescence and autophagy in liver cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a7e68558f40d00d2496644929f5edcaTest
https://pubmed.ncbi.nlm.nih.gov/23518600Test

المؤلفون: Zhe Li, Su Mi, Fang Hua, Hong Liu, Zhuo-Wei Hu

المصدر: Autophagy. 9(5)

مصطلحات موضوعية: Class I Phosphatidylinositol 3-Kinases, Pulmonary Fibrosis, Biology, Bleomycin, Glycogen Synthase Kinase 3, Mice, Phosphatidylinositol 3-Kinases, Phosphoserine, GSK-3, immune system diseases, hemic and lymphatic diseases, Pulmonary fibrosis, medicine, Autophagy, Animals, Humans, Cycloheximide, Phosphorylation, Molecular Biology, neoplasms, Lung, PI3K/AKT/mTOR pathway, Glycogen Synthase Kinase 3 beta, Kinase, Protein Stability, Interleukin-17, Ubiquitination, Membrane Proteins, Epithelial Cells, Cell Biology, BECN1, medicine.disease, Basic Research Paper, Cell biology, Enzyme Activation, Proto-Oncogene Proteins c-bcl-2, Proteolysis, Cancer research, Beclin-1, Signal transduction, Apoptosis Regulatory Proteins, Protein Binding

الوصف: We recently found that activation of IL17A signaling promotes the development and progression of acute and chronic pulmonary fibrosis, and that the blockade of IL17A activity attenuates pulmonary fibrosis by promoting the resolution of inflammation and the activation of autophagy. Although the induction of autophagy stimulating the collagen degradation in the fibrotic lung tissue has been identified as a mechanism responsible for the antifibrotic role of targeting IL17A, it remains to be clarified how IL17A signaling suppresses autophagy. Here we report that the phosphorylation of B-cell CLL/lymphoma 2 (BCL2), an apoptosis regulatory protein, was inhibited in the presence of IL17A in lung epithelial cells, and this reduction suppressed the ubiquitination degradation of BCL2, which subsequently attenuated autophagy by promoting the interaction of BCL2 and BECN1. We found that IL17A regulated the phosphorylation of BCL2 through activating the phosphoinositide 3-kinase (PI3K)-glycogen synthase kinase 3 β (GSK3B) signaling cascade. In response to IL17A stimulation, PI3K was activated and resulted in phosphorylation of GSK3B at Ser9, which subsequently attenuated the interaction of GSK3B with BCL2. Interrupting the GSK3B and BCL2 interaction precluded the phosphorylation of BCL2 at Ser70, which could trigger the ubiquitination degradation, and restrained the ubiquitination degradation of BCL2. Consequently, a decrease in the BCL2 degradation induced by IL17A resulted in a suppressed autophagy in lung epithelial cells. These findings indicate that the IL17A-PI3K-GSK3B-BCL2 signaling pathway participates in the attenuation of autophagic activity in lung epithelial cells, which is attributed to be primarily responsible for the development and progression of IL17A-induced pulmonary fibrosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d82493597f3c4508fbddb6f1c30c6450Test
https://pubmed.ncbi.nlm.nih.gov/23514933Test

المؤلفون: Heng Lin, Zi Yan Wang, Xiao Xi Lv, Jun Yan, Jian Fei Xue, Qi Lv, Hong-Zhen Yang, Jin Wen Liu, Fang Hua, Zhuo-Wei Hu

المصدر: FEBS letters. 584(14)

مصطلحات موضوعية: Death Domain Receptor Signaling Adaptor Proteins, Biophysics, DEDD, Apoptosis, Biology, Biochemistry, Transforming Growth Factor beta1, Mice, Invasion, Structural Biology, Transcription (biology), TGF-β1, Genetics, Animals, Phosphorylation, Molecular Biology, Gene, Cancer, integumentary system, Effector, Cell Differentiation, Cell Biology, Cell biology, DNA-Binding Proteins, Cancer research, biological phenomena, cell phenomena, and immunity, Signal transduction, Smad3, Transforming growth factor, Signal Transduction

الوصف: Transforming growth factor-β1 (TGF-β1) regulates a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Here we report that death effector domain-containing DNA-binding protein (DEDD) physically interacts with Smad3. The inhibition of Smad3 by DEDD resulted in a reduction in TGF-β1/Smad3-mediated transcription. DEDD inhibited the functions of Smad3 by preventing Smad3 phosphorylation, which led to the reduced expression of TGF-β1/Smad3-targeted genes. TGF-β1 inhibited DEDD expression, and DEDD inhibited TGF-β1-mediated invasion. Therefore, our findings suggest that through its interaction with Smad3, DEDD is a novel negative regulator of the TGF-β1 signaling pathway. Structured summary MINT- 7895480 : DEDD (uniprotkb: O75618 ) physically interacts (MI: 0915 ) with Smad3 (uniprotkb: P84022 ) by anti bait co-immunoprecipitation (MI: 0006 )

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b16b20a996ce945814ca23418da68dbfTest
https://pubmed.ncbi.nlm.nih.gov/20553715Test