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

descriptionPublicationkeyboard_double_arrow_right Article 06 Apr 2007 English Publisher:American Association for the Advancement of Science (AAAS)Journal:Science, volume 316, pages 109-112 (issn: 0036-8075, eissn: 1095-9203,

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Authors: Young-Sam, Lee; Sashidhar, Mulugu; John D, York; Erin K, O'Shea;

doi: 10.1126/science.1139080

pmid: 17412959

pmc: PMC2211727

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

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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 (IP 7 ) as a cellular component that stimulates Pho81-dependent inhibition of Pho80-Pho85. IP 7 is necessary for Pho81-dependent inhibition of Pho80-Pho85 in vitro. Moreover, intracellular concentrations of IP 7 increased upon phosphate starvation, and yeast mutants defective in IP 7 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.

Related Organizations

Harvard University
United States
Duke Medical Center
United States
Howard Hughes Medical Institute
United States

Keywords

Cell Nucleus, Phosphotransferases (Phosphate Group Acceptor), Saccharomyces cerevisiae Proteins, Inositol Phosphates, Saccharomyces cerevisiae, Cyclin-Dependent Kinases, Recombinant Proteins, DNA-Binding Proteins, Repressor Proteins, Cyclins, Signal Transduction, Transcription Factors

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