Recent developments in cyclin-dependent kinase biochemical and structural studies

被引：102

作者：

Echalier, Aude ^{[1
]}

Endicott, Jane A. ^{[1
]}

Noble, Martin E. M. ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Lab Mol Biophys, Oxford OX1 3QU, England

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2010年 / 1804卷 / 03期

基金：

英国医学研究理事会;

关键词：

CDK; Cyclin; Cell cycle regulation; X-ray crystallography; MAMMALIAN-CELL-CYCLE; SUBSTRATE RECOGNITION; CRYSTAL-STRUCTURE; CDK INHIBITORS; SPECIFICITY DETERMINANTS; RECRUITMENT PEPTIDES; INK4; INHIBITORS; DNA-DAMAGE; T-LOOP; COMPLEX;

D O I：

10.1016/j.bbapap.2009.10.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：511 / 519

页数：9

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