IDENTIFICATION OF HUMAN CYCLIN-DEPENDENT KINASE-8, A PUTATIVE PROTEIN-KINASE PARTNER FOR CYCLIN-C

Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G(1) cyclin functio n, This suggested that cyclin C might play a role in cell cycle contro l, but progress toward understanding the function of this cyclin has b een hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyc lin-dependent kinase 8 (CDK8)], that is likely to be a physiological p artner of cyclin C, A specific interaction between K35 and cyclin C co uld be demonstrated after translation of CDKs and cyclins in vitro. Fu rthermore, cyclin C could be detected in K35 immunoprecipitates prepar ed from HeLa cells, indicating that the two proteins form a complex al so in vivo. The K35-cyclin C complex is structurally related to SRB10- SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymera se II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CD K8)-cyclin C might be functionally associated with the mammalian trans cription apparatus, perhaps involved in relaying growth-regulatory sig nals.