Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity
Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity
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DOI：
10.1038/sj.onc.1204129
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发表时间：
2001-02-01
期刊：
影响因子：
8
通讯作者：
Piette, J
中科院分区：
文献类型：
--
作者：
Barette, C;Jariel-Encontre, I;Piette, J
细胞周期蛋白C属于细胞周期蛋白家族，通过激活特定的催化亚基，即细胞周期蛋白依赖性激酶（CDKs）来控制细胞周期转变。然而，目前还没有证据表明细胞周期蛋白C及其伴侣cdk8在细胞周期调节中起任何作用。相反，细胞周期蛋白C-cdk8复合物被发现与RNA聚合酶II转录机制相关。真正细胞周期蛋白的周期性降解对细胞周期进程至关重要，并取决于相关CDK的催化活性。我们发现内源性的cyclin C非常稳定，半衰期为4小时，相比之下，外源性表达的cyclin C非常不稳定（半衰期为15分钟），并通过泛素-蛋白酶体途径降解。然而，与其相关的cdk共表达强烈地稳定了细胞周期蛋白C，并导致蛋白质半衰期接近内源性细胞周期蛋白C。与其他细胞周期蛋白家族成员的数据形成鲜明对比，催化活性和非活性cdk8都能诱导细胞周期蛋白C稳定。此外，在这两种情况下，这种稳定都伴随着细胞周期蛋白的磷酸化，当不稳定时无法检测到。我们的研究结果表明，细胞周期蛋白C在其CDK伴侣对其稳定性的调节方面明显不同于其他细胞周期蛋白。
Cyclin C belongs to the cyclin family of proteins that control cell cycle transitions through activation of specific catalytic subunits, the cyclin-dependent kinases (CDKs), However, there is as yet no evidence, for any role of cyclin C and its partner, cdk8, in cell cycle regulation. Rather, the cyclin C-cdk8 complex was found associated with the RNA polymerase II transcription machinery. The periodic degradation of bona fide cyclins is crucial for cell-cycle progression and depends on the catalytic activity of the associated CDK. Here we,ve show that endogenous cyclin C protein is quite stable with a half-life of 4 h, In contrast, exogenously expressed cyclin C is very unstable (half-life 15 min) and degraded by the ubiquitin-proteasome pathway. Co-expression with its associated cdk, however, strongly stabilizes cyclin C and results in a protein half-life near that of endogenous cyclin C. In stark contrast to data reported for other members of the cyclin family, both catalytically active and inactive cdk8 induce cyclin C stabilization. Moreover, this stabilization is accompanied in both cases by phosphorylation of the cyclin,which is not detectable when unstable. Our results indicate that cyclin C has apparently diverged from other cyclins in the regulation of its stability by its CDK partner.