Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity

Cyclin C belongs to the cyclin family of proteins that control cell cycle t ransitions through activation of specific catalytic subunits, the cyclin-de pendent 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 cy clin C-cdk8 complex was found associated with the RNA polymerase II transcr iption machinery. The periodic degradation of bona fide cyclins is crucial for cell-cycle progression and depends on the catalytic activity of the ass ociated CDK. Here we,ve show that endogenous cyclin C protein is quite stab le 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 p athway. 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 fami ly, both catalytically active and inactive cdk8 induce cyclin C stabilizati on. Moreover, this stabilization is accompanied in both cases by phosphoryl ation of the cyclin,which is not detectable when unstable. Our results indi cate that cyclin C has apparently diverged from other cyclins in the regula tion of its stability by its CDK partner.