The CDK Pho85 Inhibits Whi7 Start Repressor to Promote Cell Cycle Entry in Budding Yeast

Pho85 is a multifunctional CDK that signals to the cell when environmental conditions are favorable. It has been connected to cell cycle control, mainly in Start where it promotes the G1/S transition. Here we describe that the Start repressor Whi7 is a key target of Pho85 in the regulation of cell cycle entry. The phosphorylation of Whi7 by Pho85 inhibits the repressor and explains most of the contribution of the CDK in the activation of Start. Mechanistically, Pho85 downregulates Whi7 protein levels through the control of Whi7 protein stability and WHI7 gene transcription. Whi7 phosphorylation by Pho85 also restrains the intrinsic ability of Whi7 to associate with promoters. Furthermore, although Whi5 is the main Start repressor in normal cycling cells, in the absence of Pho85, Whi7 becomes the major repressor leading to G1 arrest. Overall, our results reveal a novel mechanism by which Pho85 promotes Start through the regulation of the Whi7 repressor at multiple levels, which may confer to Whi7 a functional specialization to connect the response to adverse conditions with the cell cycle control.