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Science 6 April 2007: Vol. 316. no. 5821, pp. 109 - 112 DOI: 10.1126/science.1139080
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Reports
Regulation of a Cyclin-CDK-CDK Inhibitor Complex by Inositol Pyrophosphates
Young-Sam Lee,1
Sashidhar Mulugu,2
John D. York,2
Erin K. O'Shea1*
In budding yeast, phosphate starvation triggers inhibition of the Pho80-Pho85 cyclincyclin-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.
1 Howard Hughes Medical Institute, Faculty of Arts and Sciences Center for Systems Biology, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
2 Howard Hughes Medical Institute, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
* To whom correspondence should be addressed. E-mail: erin_oshea{at}harvard.edu
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