作者
Stéphane Larochelle, Karl A Merrick, Marie-Emilie Terret, Lara Wohlbold, Nora M Barboza, Chao Zhang, Kevan M Shokat, Prasad V Jallepalli, Robert P Fisher
发表日期
2007/3/23
期刊
Molecular cell
卷号
25
期号
6
页码范围
839-850
出版商
Elsevier
简介
Cell division is controlled by cyclin-dependent kinases (CDKs). In metazoans, S phase onset coincides with activation of Cdk2, whereas Cdk1 triggers mitosis. Both Cdk1 and -2 require cyclin binding and T loop phosphorylation for full activity. The only known CDK-activating kinase (CAK) in metazoans is Cdk7, which is also part of the transcription machinery. To test the requirements for Cdk7 in vivo, we replaced wild-type Cdk7 with a version sensitive to bulky ATP analogs in human cancer cells. Selective inhibition of Cdk7 in G1 prevents activation (but not formation) of Cdk2/cyclin complexes and delays S phase. Inhibiting Cdk7 in G2 blocks entry to mitosis and disrupts Cdk1/cyclin B complex assembly, indicating that the two steps of Cdk1 activation—cyclin binding and T loop phosphorylation—are mutually dependent. Therefore, by combining chemical genetics and homologous gene replacement in somatic cells …
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S Larochelle, KA Merrick, ME Terret, L Wohlbold… - Molecular cell, 2007