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

Young Sam Lee; Sashidhar Mulugu; John D. York; Erin K. O'Shea

doi:10.1126/science.1139080

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

Young Sam Lee, Sashidhar Mulugu, John D. York, Erin K. O'Shea

Molecular and Cellular Biochemistry

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229 Scopus citations

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. IP ₇ 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.

Original language	English
Pages (from-to)	109-112
Number of pages	4
Journal	Science
Volume	316
Issue number	5821
DOIs	https://doi.org/10.1126/science.1139080
State	Published - Apr 6 2007

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title = "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. IP 7 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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AU - Lee, Young Sam

AU - Mulugu, Sashidhar

AU - York, John D.

AU - O'Shea, Erin K.

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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. IP 7 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.

AB - 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. IP 7 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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Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates

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