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Regulation of a Cyclin-CDK-CDK Inhibitor Complex by Inositol Pyrophosphates

2007; American Association for the Advancement of Science; Volume: 316; Issue: 5821 Linguagem: Inglês

10.1126/science.1139080

1095-9203

Young‐Sam Lee, Sashidhar Mulugu, John D. York, Erin K. O’Shea,

Microtubule and mitosis dynamics

In budding yeast, phosphate starvation triggers inhibition of the Pho80-Pho85 cyclin-cyclin-dependent kinase (CDK) complex by the CDK inhibitor Pho81, leading to expression of genes involved in nutrient homeostasis. We isolated myo-d-inositol heptakisphosphate (IP7) as a cellular component that stimulates Pho81-dependent inhibition of Pho80-Pho85. IP7 is necessary for Pho81-dependent inhibition of Pho80-Pho85 in vitro. Moreover, intracellular concentrations of IP7 increased upon phosphate starvation, and yeast mutants defective in IP7 production failed to inhibit Pho80-Pho85 in response to phosphate starvation. These observations reveal regulation of a cyclin-CDK complex by a metabolite and suggest that a complex metabolic network mediates signaling of phosphate availability.