The Role of PP2A in Yeast Cell Cycle Progression

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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.