Leclerc V, Tassan J P, O'Farrell P H, Nigg E A, Léopold P
URA 671 Centre National de la Recherche Scientifique, Villefranche-sur-mer, France.
Mol Biol Cell. 1996 Apr;7(4):505-13. doi: 10.1091/mbc.7.4.505.
A number of cyclins have been described, most of which act together with their catalytic partners, the cyclin-dependent kinases (Cdks), to regulate events in the eukaryotic cell cycle. Cyclin C was originally identified by a genetic screen for human and Drosophila cDNAs that complement a triple knock-out of the CLN genes in Saccharomyces cerevisiae. Unlike other cyclins identified in this complementation screen, there has been no evidence that cyclin C has a cell-cycle role in the cognate organism. Here we report that cyclin C is a nuclear protein present in a multiprotein complex. It interacts both in vitro and in vivo with Cdk8, a novel protein-kinase of the Cdk family, structurally related to the yeast Srb10 kinase. We also show that Cdk8 can interact in vivo with the large subunit of RNA polymerase II and that a kinase activity that phosphorylates the RNA polymerase II large subunit is present in Cdk8 immunoprecipitates. Based on these observations and sequence similarity to the kinase/cyclin pair Srb10/Srb11 in S. cerevisiae, we suggest that cyclin C and Cdk8 control RNA polymerase II function.
现已发现多种细胞周期蛋白，其中大多数与它们的催化伴侣——细胞周期蛋白依赖性激酶（Cdk）共同作用，以调控真核细胞周期中的各种事件。细胞周期蛋白C最初是通过对人类和果蝇cDNA进行遗传筛选而鉴定出来的，这些cDNA可互补酿酒酵母中CLN基因的三重敲除。与在此互补筛选中鉴定出的其他细胞周期蛋白不同，尚无证据表明细胞周期蛋白C在同源生物体中具有细胞周期作用。在此我们报告，细胞周期蛋白C是一种存在于多蛋白复合物中的核蛋白。它在体外和体内均与Cdk8相互作用，Cdk8是Cdk家族的一种新型蛋白激酶，在结构上与酵母Srb10激酶相关。我们还表明，Cdk8在体内可与RNA聚合酶II的大亚基相互作用，并且在Cdk8免疫沉淀产物中存在使RNA聚合酶II大亚基磷酸化的激酶活性。基于这些观察结果以及与酿酒酵母中激酶/细胞周期蛋白对Srb10/Srb11的序列相似性，我们认为细胞周期蛋白C和Cdk8可控制RNA聚合酶II的功能。
