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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lee, Y-S; Mulugu, S; York, JD; O'Shea, EK

Published Date

  • April 6, 2007

Published In

Volume / Issue

  • 316 / 5821

Start / End Page

  • 109 - 112

PubMed ID

  • 17412959

Pubmed Central ID

  • PMC2211727

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1139080


  • eng

Conference Location

  • United States