Multiple Pho85-Dependent Mechanisms Control G1 Cyclin Abundance in Response to Nutrient Stress

Availability of nutrients is an important prerequisite for cellproliferation. The stress signals caused by lack of nutrients affect cell cycle decisions causing the cell to arrest in G1 and enter the G0 phase. However, the direct molecular links connecting these stress signals to cell cycle control are not yet well established. The core coordinator of cell cycle progression is cyclin-dependent kinase (CDK). In budding yeast, the activation of Cdk1 by rising levels of the G1-specific cyclin Cln3 (the mammalian analog is cyclin D1) triggers phosphorylation and inactivation of the tran-scriptional repressor Whi5 (the mammalian analog is pRb) (1). Phosphorylation of Whi5 initiates the transcription of nearly 200 cell cycle-related genes, including the cyclins Cln1 and Cln2 that further activate Cdk1 to accelerate Whi5 inactivation (2). The level of Cln3must surpass a certain threshold for cell cycle Start to take place. Its level is determined by the rates of Cln3 synthesis and degradation. Therefore, degradation pathways for Cln3 are a pos