Coordination mechanisms of stress response with cell cycle regulation by the yeast Pho85 kinase

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When yeast cells encounter environmental stress, progression through the cell cycle is delayed, providing time for adaptation to the stress conditions. We found that CLN2 was downregulated under alkaline conditions, and that the Pho85-Pho80 complex was required to sustain CLN2 expression under alkaline conditions. We also found that Pho4 is necessary for adaptation to alkaline conditions, possibly by activating Ptk2. The alkaline stress signal was transmitted through Pho81 CKI to repress the Pho85-Pho80 activity, which leads to activation of transcription factors Pho4, Rim101, and Crz1, all of which inhibited CLN2 expression when overproduced. Whi5 represses CLN2 expression, and CLN2 expression level in a pho85 pho4 rim101 crz1 quadruple deletion mutant was stimulated when the Whi5 activity was repressed by overproduction of Pho85-Pcl9. Rpd3 is involved in CLN2 repression by these factors.