MOLECULAR INTERACTIONS AND SUBSTRATES OF MAMMALIAN SIRT6 LONGEVITY REGULATOR

哺乳动物 SIRT6 寿命调节剂的分子相互作用和底物

• 批准号: 8363767
• 负责人: Katrin F Chua
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363767
• 关键词: Age; Aging; Animal Model; Attenuated; Binding; Biochemical; Biochemistry; Biological Process; Cells; Cellular biology; Drosophila genus; Funding; Genome Stability; Genomic Instability; Genomics; Grant; Health; Homologous Gene; Human; Learning; Link; Longevity; Macromolecular Complexes; Malignant Neoplasms; Mass Spectrum Analysis; Metabolism; Molecular; Mus; National Center for Research Resources; Pathology; Pathway interactions; Principal Investigator; Protein Binding; Proteins; Proteomics; Regulation; Research; Research Infrastructure; Resources; Series; Source; United States National Institutes of Health; Work; cost; fly; link protein; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Sir2 (Silent Information Regulator-2) proteins link aging and lifespan regulation, genomic stability, and metabolism in multiple model organisms. Recent work indicates that mammalian Sir2 protein SIRT6 suppresses genomic instability and attenuates the onset of several age-associated pathologies. SIRT7, a closely related protein, has also been linked to aging in some mouse studies. However, much remains to be learned about the molecular mechanisms of SIRT6 and SIRT7 function. Our work focuses on a systematic characterization of the basic molecular mechanisms through which SIRT6 and SIRT7 function, using a combination of biochemistry and cell biology in human cells, genomic and proteomic analyses, and complementary studies of the SIRT6 and SIRT7 homologs in drosophila flies. This work will be instrumental for elucidating fundamental biological processes that impact on human health and aging, cancer, and metabolism. A series of biochemical, cellular, and global proteomic and genomic analyses are being carried out to define the molecular functions of SIRT6 and SIRT7 in mammalian and drosophila cells. We propose: 1. To elucidate novel mammalian SIRT6 and SIRT7 regulated molecular pathways. Proteomic and biochemical approaches are taken to isolate and identify SIRT6 substrates, protein binding partners, and macromolecular complexes. 2. To elucidate novel molecular pathways regulated by drosophila dSIRT6 and dSIRT7. Proteomic and biochemical approaches are taken to isolate and identify their substrates, protein binding partners, and macromolecular complexes. Mass Spectrometry analysis with the UCSF Mass Spectrometry Facility will be essential for these aims.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 Sir2（沉默信息调节器-2）蛋白将多种模型生物体中的衰老和寿命调节、基因组稳定性和新陈代谢联系起来。 最近的研究表明，哺乳动物 Sir2 蛋白 SIRT6 可以抑制基因组不稳定性并减轻多种与年龄相关的病理的发生。 SIRT7 是一种密切相关的蛋白质，在一些小鼠研究中也与衰老有关。然而，关于 SIRT6 和 SIRT7 功能的分子机制还有很多有待了解。 我们的工作重点是结合人类细胞中的生物化学和细胞生物学、基因组和蛋白质组分析以及果蝇中 SIRT6 和 SIRT7 同源物的补充研究，系统地表征 SIRT6 和 SIRT7 发挥功能的基本分子机制。这项工作将有助于阐明影响人类健康、衰老、癌症和新陈代谢的基本生物过程。 正在进行一系列生化、细胞和整体蛋白质组学和基因组分析，以确定 SIRT6 和 SIRT7 在哺乳动物和果蝇细胞中的分子功能。 我们建议： 1. 阐明新的哺乳动物 SIRT6 和 SIRT7 调节分子途径。 采用蛋白质组学和生化方法来分离和鉴定 SIRT6 底物、蛋白质结合伴侣和大分子复合物。 2. 阐明果蝇dSIRT6和dSIRT7调控的新分子途径。 采用蛋白质组学和生化方法来分离和鉴定其底物、蛋白质结合配偶体和大分子复合物。 使用加州大学旧金山分校质谱设施进行质谱分析对于实现这些目标至关重要。