Recent developments in cyclin-dependent kinase biochemical and structural studies
Recent developments in cyclin-dependent kinase biochemical and structural studies
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DOI：
10.1016/j.bbapap.2009.10.002
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发表时间：
2010-03-01
影响因子：
3.2
通讯作者：
Noble, Martin E. M.
中科院分区：
文献类型：
--
作者：
Echalier, Aude;Endicott, Jane A.;Noble, Martin E. M.
细胞周期蛋白依赖性激酶（CDKs）因其参与调节细胞增殖和转录等基本细胞活动而受到广泛研究。一系列含有cdk2的结构为CDK活化和调控的分子细节提供了一个通用模型。最近对CDK家族其他成员的结构研究导致了对该模型的重新评估。在这篇综述中，我们以最近表征的CDK/cyclin复合物，CDK9/cyclinT1和CDK4/cyclinD为例，描述了其他CDK-cyclin组装体。根据CDK2/cyclinA、CDK9/cyclinT、CDK4/cyclinD和Pho85/Pho80的最新数据，研究了CDK磷酸化对CDK激活状态和底物特异性的差异影响。我们还概述了影响CDK底物特异性的因素，特别是细胞周期蛋白亚基的贡献。最后，我们回顾了最近的研究结果，这些结果有助于揭示Cip/Kip CDK抑制剂家族在CDK调控中相互冲突的分子机制。(C) 2009 Elsevier B.V.版权所有
The cyclin-dependent kinases (CDKs) have been intensely studied because of their involvement in regulating essential cellular activities that include proliferation and transcription. A series of CDK2-containing structures have informed a general model for the molecular details of CDK activation and regulation. Recent structural studies of other members of the CDK family have lead to a re-appraisal of this model. In this review, we describe alternative CDK-cyclin assemblies taking the recently characterised CDK/cyclin complexes, CDK9/cyclinT1 and CDK4/cyclinD as examples. The differential effects of CDK phosphorylation on CDK activation state and substrate specificity are examined in the light of recent data on CDK2/cyclinA, CDK9/cyclinT, CDK4/cyclinD and Pho85/Pho80. We also present an overview of factors that affect CDK substrate specificity, and, in particular, the contributions that are made by the cyclin subunit. Finally, we review recent results that have helped to unravel the molecular mechanisms underlying the conflicting roles of the Cip/Kip CDK inhibitor family in CDK regulation. (C) 2009 Elsevier B.V. All rights reserved.