Coupling Cell Cycle Progression to Cell Morphogenesis

描述（由申请人提供）：胞苷肽是在从酵母到人类的真核细胞谱系中普遍存在的GTP结合和促凋亡形成蛋白。隔膜蛋白参与涉及膜和细胞骨架结构重塑的细胞过程，特别是在细胞分裂和胞质分裂期间。在芽殖酵母（酿酒酵母）中，septin丝组装在协调细胞周期事件中起着重要作用，部分是通过在母细胞和其子细胞之间的发育界面（芽颈）建立用于招募和相互作用的众多蛋白激酶的支架。Hsl 1是AMPK相关蛋白激酶家族的成员，位于芽颈处，并整体参与耦联隔蛋白项圈组装以进入M期的许可。该提案描述了实验方法，以解决目前知之甚少的Hsl 1介导的信号传导的三个领域：（1）什么因素是必要的Hsl 1激活？(2)Hsl 1介导的新靶点和已建立靶点的磷酸化在退出检查点中起什么作用？(3)HsM的泛素相关结构域（DBA）在其活性、定位和/或稳定性中起什么作用？

DESCRIPTION (provided by applicant): Septins are GTP-binding and filament-forming proteins found ubiquitously in the eukaryotic lineage that spans from yeasts to humans. Septins participate in cellular processes that involve remodeling of membranes and cytoskeletal structures, especially during cell division and cytokinesis. In budding yeast (Saccharomyces cerevisiae), septin filament assembly serves a prominent role in coordinating cell cycle events, in part, by establishing a scaffold for recruitment and interaction of numerous protein kinases at the developing interface (bud neck) between a mother cell and its daughter cell. Hsl1, a member of the family of AMPK-related protein kinases, is located at the bud neck and is integrally involved in coupling septin collar assembly to licensing of entry into M phase. This proposal describes experimental approaches to address three areas of Hsl1-mediated signaling that are currently poorly understood: (1) What factors are necessary for Hsl1 activation? (2) What role does Hsl1-mediated phosphorylation of new and established targets play in exit from the checkpoint? (3) What function does the ubiquitin-associated domain (DBA) of HsM play in its activity, localization, and/or stability?