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Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates.

ABSTRACT: 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.

SUBMITTER: Lee YS

PROVIDER: S-EPMC2211727 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates.

Lee Young-Sam YS Mulugu Sashidhar S York John D JD O'Shea Erin K EK

Science (New York, N.Y.) 20070401 5821

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 starva ...[more]

PMID: 17412959

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