Role of the NCoR corepressor complex in the development of insulin resistance

NCoR 辅阻遏物复合物在胰岛素抵抗发展中的作用

• 批准号: 8149970
• 负责人: VALENTINA PERISSI
• 金额: $ 24.65万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-25 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8149970
• 关键词: Adipocytes; Award; Binding; Biochemical; Biological Assay; Cells; Characteristics; Chemicals; Complex; Cytoplasm; Data; Defect; Development; Diabetes Mellitus; Down-Regulation; Enzymes; Excision; Future; GPS2 gene; GTP-Binding Proteins; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Goals; Grant; Human; Inflammation; Inflammatory; Inflammatory Response; Insulin; Insulin Resistance; Insulin Signaling Pathway; Knockout Mice; Knowledge; Lead; Light; Link; Location; MAPK8 gene; Mediating; Metabolic Diseases; Molecular; NF-kappa B; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Nuclear Receptors; Obesity; Pathway interactions; Phase; Phenotype; Phosphorylation; Phosphotransferases; Physiological; Play; Principal Investigator; Process; Production; Progress Reports; Protein Kinase; Proteins; Reactive Oxygen Species; Recruitment Activity; Regulation; Regulatory Element; Research; Role; Series; Serine; Signal Transduction; Small Interfering RNA; Stimulus; Stress; Testing; Transcription Repressor/Corepressor; Transcriptional Activation; Transcriptional Regulation; Ubiquitin-Conjugating Enzymes; Update; base; blood glucose regulation; cofactor; diabetic; genome-wide; improved; in vivo; in vivo Model; inhibitor/antagonist; insulin signaling; mouse model; novel; overexpression; programs; promoter; research study; response; transcription factor

PROGRESS REPORT AND UPDATED RESEARCH PLAN The main goal of this grant was to investigate the role of a transcriptional cofactor, GPS2, and its novel interacting partner, NEURL4/KIAA1787, in obesity-associated inflammatory responses and in the development of insulin resistance. Our original hypothesis was that these two proteins could play a key inhibitory role during the physiological response to insuHn signaling by keeping the NFKB and APi signaling network under negative control in the absence of stimulatory signals. The loss or downregulation of such inhibition may participate in the development of obesity-induced insulin resistance. Three Specific Aims were proposed: i) To define GPS2-dependent gene networks in adipocytes; ii) To investigate the molecular mechanism of GPS2 and KIAA1787 functions in inhibiting JNK-mediated signaling and regulating transcriptional activation mediated by NFKB and APi transcription factors; iii) To test in vivo whether GPS2 and KIAA1787 are relevant for the development of insulin resistance by creating null mice models. Here, for each Aim, I will discuss the progresses made during the K99 phase of the award and describe the future experiments as the original plans have been updated in light ofthe current results.

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