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 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.
Barette
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C
Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, IFR24, 1919, route de Mende, 34293 Montpellier Cedex 5, France.
Jariel-Encontre
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I
Piechaczyk
M
M
Piette
J
J
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002384:Catalysis; D056745:Cyclin C; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004355:Drug Stability; D005786:Gene Expression Regulation; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
C503674:CCNC protein, human; C503675:Ccnc protein, mouse; D056745:Cyclin C; D016213:Cyclins; D009097:Multienzyme Complexes; D014452:Ubiquitins; D017346:Protein Serine-Threonine Kinases; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex