The timing and order of cell cycle progression is regulated by cyclin-dependent kinases (CDKs) to ensure accurate duplication of the genome and other cell components. In budding yeast, accumulation of the cyclin Cln3 (homolog of meta-zoan Cyclin D) during G_1 activates the major CDK Cdkl (homolog of CDK4, CDK2 and CDC2). The active Cdkl-Cln3 complex induces expression of late G_1 cyclins (homologs of Cyclins E) that further activate Cdkl to drive cells to pass START and initiate DNA replication in S phase. Since Cln3 levels fail to increase upon starvation, both the expression and stability of Cln3 have long been implicated as targets of nutrient signaling. Nonetheless, specific mechanisms by which nutrient signals impinge on the cell cycle machinery have yet to be defined. Recent studies by our groups revealed that nitrogen and phosphate availability regulate distinct phosphorylations that determine Cln3 stability. Both signals are mediated by activation of a second CDK, Pho85, though via different cyclins that have distinct effects on the cell cycle. Thus, the two studies converge to suggest a remarkably complex regulation of the CDK-cyclin system in response to nutrient levels.
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