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Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates.
Science. 2007 Apr 06; 316(5821):109-12.Sci

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.

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Authors+Show Affiliations

Lee YS
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.
Mulugu S
No affiliation info available
York JD
No affiliation info available
O'Shea EK
No affiliation info available

MeSH

Cell NucleusCyclin-Dependent KinasesCyclinsDNA-Binding ProteinsInositol PhosphatesPhosphotransferases (Phosphate Group Acceptor)Recombinant ProteinsRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionTranscription Factors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17412959

Citation

Lee, Young-Sam, et al. "Regulation of a cyclin-CDK-CDK Inhibitor Complex By Inositol Pyrophosphates." Science (New York, N.Y.), vol. 316, no. 5821, 2007, pp. 109-12.
Lee YS, Mulugu S, York JD, et al. Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science. 2007;316(5821):109-12.
Lee, Y. S., Mulugu, S., York, J. D., & O'Shea, E. K. (2007). Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science (New York, N.Y.), 316(5821), 109-12.
Lee YS, et al. Regulation of a cyclin-CDK-CDK Inhibitor Complex By Inositol Pyrophosphates. Science. 2007 Apr 6;316(5821):109-12. PubMed PMID: 17412959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. AU - Lee,Young-Sam, AU - Mulugu,Sashidhar, AU - York,John D, AU - O'Shea,Erin K, PY - 2007/4/7/pubmed PY - 2007/4/18/medline PY - 2007/4/7/entrez SP - 109 EP - 12 JF - Science (New York, N.Y.) JO - Science VL - 316 IS - 5821 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/17412959/Regulation_of_a_cyclin_CDK_CDK_inhibitor_complex_by_inositol_pyrophosphates_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=17412959 DB - PRIME DP - Unbound Medicine ER -