The Role of PP2A in Yeast Cell Cycle Progression

PP2A 在酵母细胞周期进展中的作用

基本信息

批准号：
7581085
负责人：
YU JIANG
金额：
$ 22.53万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2011-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Protein phosphatase 2A is a major protein ser/thr phosphatase in eukaryotes, whose activity has been implicated in numerous cellular processes. The PP2A holoenzyme is a heterotrimeric protein complex that is comprised of one catalytic subunit (PP2Ac) and two regulatory subunits (A and B). However, recent studies in both yeast and mammalian cells have identified a novel PP2A complex that contains the catalytic subunit and a cellular protein, named Tap42 in yeast and a-4 protein in mammals. In yeast, the Tap42-PP2Ac complex is part of the TOR signaling pathway, and has been shown to be essential for cell growth. However, the essential role for this complex in controlling cell growth and proliferation is unknown. In our preliminary study, we found that the Tap42-PP2Ac complex was involved in controlling the actin cytoskeleton, cell wall integrity and the G2/M transition during the cell cycle, three events that were previously believed to be controlled by the PP2A holoenzyme. This finding suggests new interpretations for the role of PP2A in these processes, and offers new clues for dissecting the mechanisms by which PP2A regulates these processes. Based on the results of our preliminary studies, we propose the following specific aims to examine the role of the Tap42-PP2Ac in these processes: Specific Aim 1. To test the hypothesis that Rom2 is the direct target of the Tap42-PP2Ac complex in the cell wall integrity pathway. Specific Aim 2. To examine the putative feedback mechanism by which Mpk1 downregluates the cell wall integrity pathway. Specific Aim 3. To test the hypothesis that the Tap42-PP2Ac complex controls the G2 gene expression through the Fkh1/2 transcription factors. This study is part of our long-term goals to understand the role of PP2A in cell growth control.

描述（由申请人提供）：蛋白质磷酸酶2a是真核生物中主要的蛋白质Ser/Thr磷酸酶，其活性已与许多细胞过程有关。 PP2A全酶是一种异三聚体蛋白质复合物，由一个催化亚基（PP2AC）和两个调节亚基（A和B）组成。然而，最近在酵母菌和哺乳动物细胞中的研究已经鉴定出一种新型的PP2A复合物，其中包含催化亚基和细胞蛋白，在酵母中命名为TAP42，在哺乳动物中命名为A-4蛋白。在酵母中，TAP42-PP2AC复合物是TOR信号通路的一部分，已被证明对于细胞生长至关重要。但是，该复合物在控制细胞生长和增殖中的重要作用尚不清楚。在我们的初步研究中，我们发现TAP42-PP2AC复合物参与控制肌动蛋白细胞骨架，细胞壁完整性和在细胞周期中的G2/M转变，这是以前认为由PP2A Holoenzyme控制的三个事件。这一发现为PP2A在这些过程中的作用提出了新的解释，并为剖析PP2A调节这些过程的机制提供了新的线索。根据我们的初步研究的结果，我们提出了以下特定目的，以检查TAP42-PP2AC在这些过程中的作用：特定目的1。检验ROM2是TAP42-PP2AC在细胞壁完整性途径中的直接目标。特定目的2。检查MPK1下降细胞壁完整性途径的推定反馈机制。特定目的3。为了测试TAP42-PP2AC复合物通过FKH1/2转录因子控制G2基因表达的假设。这项研究是我们了解PP2A在细胞生长控制中的作用的长期目标的一部分。