定量蛋白质组学揭示了细胞周期机制生化特异性的基础。
Quantitative proteomics reveals the basis for the biochemical specificity of the cell-cycle machinery.
机构信息
The Gurdon Institute, University of Cambridge, Cambridge, UK.
出版信息
Mol Cell. 2011 Aug 5;43(3):406-17. doi: 10.1016/j.molcel.2011.05.031.
Abstract
Cyclin-dependent kinases comprise the conserved machinery that drives progress through the cell cycle, but how they do this in mammalian cells is still unclear. To identify the mechanisms by which cyclin-cdks control the cell cycle, we performed a time-resolved analysis of the in vivo interactors of cyclins E1, A2, and B1 by quantitative mass spectrometry. This global analysis of context-dependent protein interactions reveals the temporal dynamics of cyclin function in which networks of cyclin-cdk interactions vary according to the type of cyclin and cell-cycle stage. Our results explain the temporal specificity of the cell-cycle machinery, thereby providing a biochemical mechanism for the genetic requirement for multiple cyclins in vivo and reveal how the actions of specific cyclins are coordinated to control the cell cycle. Furthermore, we identify key substrates (Wee1 and c15orf42/Sld3) that reveal how cyclin A is able to promote both DNA replication and mitosis.
摘要
细胞周期蛋白依赖性激酶构成了推动细胞周期进程的保守机制，但它们在哺乳动物细胞中是如何做到这一点的仍不清楚。为了确定细胞周期蛋白-cdk 控制细胞周期的机制，我们通过定量质谱法对细胞周期蛋白 E1、A2 和 B1 的体内相互作用因子进行了时间分辨分析。对上下文相关蛋白相互作用的全面分析揭示了细胞周期蛋白功能的时间动态，其中细胞周期蛋白-cdk 相互作用网络根据细胞周期蛋白的类型和细胞周期阶段而变化。我们的研究结果解释了细胞周期机制的时间特异性，从而为体内多个细胞周期蛋白的遗传需求提供了生化机制，并揭示了特定细胞周期蛋白的作用如何协调以控制细胞周期。此外，我们鉴定了关键的底物（Wee1 和 c15orf42/Sld3），它们揭示了细胞周期蛋白 A 如何能够促进 DNA 复制和有丝分裂。
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