Mäkelä T P, Tassan J P, Nigg E A, Frutiger S, Hughes G J, Weinberg R A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Nature. 1994 Sep 15;371(6494):254-7. doi: 10.1038/371254a0.
The eukaryotic cell cycle is regulated by the sequential activation of cyclin-dependent kinases (CDKs). CDK activation is dependent on cyclin binding and phosphorylation of a conserved threonine (T161 in Cdc2) mediated by the CDK-activating kinase CAK. A CDK-related kinase, MO15 (ref. 10), has been identified as the catalytic subunit of CAK (refs 11-13). Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein. Cyclin H is a major MO15 partner in vivo and enhances the kinase activity of MO15 towards Cdk2/cyclin A. These findings demonstrate that a cyclin/kinase complex can function as a regulator of other cyclin/kinase complexes, and suggest that cyclin/kinase cascades may exist.
真核细胞周期受细胞周期蛋白依赖性激酶(CDK)的顺序激活调控。CDK的激活依赖于细胞周期蛋白的结合以及由CDK激活激酶CAK介导的保守苏氨酸(Cdc2中的T161)的磷酸化。一种与CDK相关的激酶MO15(参考文献10)已被鉴定为CAK的催化亚基(参考文献11 - 13)。在此,我们利用酵母双杂交筛选表明一种新的人类细胞周期蛋白(细胞周期蛋白H)是与MO15相关的蛋白。细胞周期蛋白H在体内是MO15的主要伙伴,并增强MO15对Cdk2/细胞周期蛋白A的激酶活性。这些发现表明一个细胞周期蛋白/激酶复合物可以作为其他细胞周期蛋白/激酶复合物的调节因子,并提示细胞周期蛋白/激酶级联反应可能存在。