Characterization of molecular mechanisms governing budding yeast lifespan using small peptides that interact with the Anaphase Promoting Complex

使用与后期促进复合物相互作用的小肽来表征控制芽殖酵母寿命的分子机制

• 批准号: RGPIN-2017-05478
• 负责人: Harkness, Troy
• 金额: $ 4.37万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=628989
• 关键词: Characterization; molecular; mechanisms; governing; budding

Evidence is accumulating that cellular lifespan correlates to its damage repair capacity. Genetic screens in model organisms, from yeast to flies, have consistently demonstrated that genes involved in stress response networks play a decisive role in lifespan determination. Using the brewing yeast model system, we have shown that regulated cell cycle progression is tightly linked with stress response and normal longevity. Our work characterizing the Anaphase Promoting Complex (APC) in yeast, a large highly conserved complex of proteins required for the targeting of substrates for ubiquitin-dependent degradation, has described a number of novel roles and substrates for the APC. The APC is largely known to target proteins that inhibit mitotic progression and G1 maintenance for degradation. Our studies over the past 15 years, many of them NSERC funded, have shown that the APC is also required for mitotic histone deposition and post-translational modifications, stress response, genomic stability, and lifespan. Our work therefore suggests that the APC plays a central and critical role in maintaining cell vigor and ultimately lifespan,

越来越多的证据表明，细胞寿命与其损伤修复能力相关。从酵母到苍蝇的模式生物的基因筛选一直表明，参与应激反应网络的基因在寿命决定中起着决定性作用。使用酿酒酵母模型系统，我们已经表明，受调节的细胞周期进程与应激反应和正常寿命密切相关。我们的工作特征后期促进复合物（APC）在酵母中，一个大的高度保守的蛋白质复合物所需的靶向底物的泛素依赖性降解，描述了一些新的作用和底物的APC。已知APC主要靶向抑制有丝分裂进程和G1维持的蛋白质降解。我们过去15年的研究（其中许多是NSERC资助的）表明，APC也是有丝分裂组蛋白沉积和翻译后修饰、应激反应、基因组稳定性和寿命所必需的。因此，我们的工作表明，APC在维持细胞活力和最终寿命方面发挥着核心和关键作用，