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

被引：226

作者：

Lee, Young-Sam

Mulugu, Sashidhar

York, John D.

O'Shea, Erin K.

机构：

[1] Harvard Univ, Howard Hughes Med Inst, Fac Arts & Sci, Ctr Syst Biol,Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[2] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

来源：

SCIENCE | 2007年 / 316卷 / 5821期

关键词：

D O I：

10.1126/science.1139080

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：109 / 112

页数：4

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