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 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.
Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity
Barette, C.; Jariel-Encontre, I.; Piechaczyk, M.; Piette, J.
2001-02-01 / vol 20 / pages 551-62
Humans; Animals; Mice; Phosphorylation; Gene Expression Regulation; Catalysis; Ubiquitins/metabolism; Hela Cells; Drug Stability; Half-Life; COS Cells; 3T3 Cells; Proteasome Endopeptidase Complex; Cysteine Endopeptidases/metabolism; Multienzyme Complexes/metabolism; *Cyclin-Dependent Kinases; Cyclins/biosynthesis/genetics/*metabolism; Protein-Serine-Threonine Kinases/biosynthesis/genetics/*metabolism