Regulation of histone deacetylase 7 (HDAC7) activity

组蛋白脱乙酰酶 7 (HDAC7) 活性的调节

• 批准号: 6684616
• 负责人: HUNG-YING KAO
• 金额: $ 26.35万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6684616
• 关键词: HeLa cells; amidohydrolases; biological signal transduction; cell growth regulation; enzyme activity; enzyme mechanism; fluorescence microscopy; genetic regulation; genetic transcription; intracellular; neoplasm /cancer genetics; protein localization; protein protein interaction; protein transport; proteolysis; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): Many studies have indicated that aberrant recruitment of histone deacetylases (HDACs) may lead to cancer. HDACs are thought to function, in part, by regulating transcriptional activity of DNA-binding transcription factors thereby modulating the expression of a network of genes. Thus, understanding how HDACs regulate transcription and how cellular signaling controls HDAC activity will help to understand deregulated cell growth in cancer and may have therapeutic implications for cancer treatment. HDAC7 (Histone deacetylase 7) belongs to the class II HDACs that includes HDAC4, -5, -6, -9, and -10. Members of the class II HDACs distinguish themselves from class I HDACs by their restricted tissue distribution profiles and notably, their ability to shuttle between the nucleus and the cytoplasm. We hypothesize that the subcellular distribution of HDAC7 is determined by the interplay between its interacting partners. Aim I will elucidate the mechanism of nucleocytoplasmic shuttling of HDAC7. Aim II will characterize the proteolytic pathway regulating HDAC7 degradation. We also discovered that 14-3-3 proteins stabilize HDAC7. Aim III will dissect the mechanism of 14-3-3-dependent stabilization of HDAC7. A combination of fluorescence microscopy, inhibitor, and biochemical approaches will be taken to accomplish these objectives. The results from this study will determine the mechanism by which HDAC7 activity is regulated at the molecular and cellular level. Understanding how cellular signaling controls HDAC activities will help to understand deregulated cell growth in cancer and may have therapeutic implications for cancer treatment.

描述（由申请人提供）：