肌醇焦磷酸对细胞周期蛋白 - 细胞周期蛋白依赖性激酶 - 细胞周期蛋白依赖性激酶抑制剂复合物的调控
Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates.
作者信息
Lee Young-Sam, Mulugu Sashidhar, York John D, O'Shea Erin K
机构信息
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.
出版信息
Science. 2007 Apr 6;316(5821):109-12. doi: 10.1126/science.1139080.
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.
摘要
在出芽酵母中，磷酸盐饥饿会触发细胞周期蛋白依赖性激酶（CDK）抑制剂Pho81对Pho80-Pho85细胞周期蛋白-CDK复合物的抑制作用，从而导致参与营养稳态的基因表达。我们分离出了肌醇七磷酸（IP7）作为一种细胞成分，它能刺激Pho81对Pho80-Pho85的依赖性抑制作用。IP7是Pho81在体外对Pho80-Pho85进行依赖性抑制所必需的。此外，磷酸盐饥饿时细胞内IP7的浓度会升高，而在IP7产生方面存在缺陷的酵母突变体在磷酸盐饥饿时无法抑制Pho80-Pho85。这些观察结果揭示了代谢物对细胞周期蛋白-CDK复合物的调控，并表明复杂的代谢网络介导了磷酸盐可用性的信号传导。
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