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

Oncogene. 2001 Feb 1;20(5):551-62. doi: 10.1038/sj.onc.1204129.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • COS Cells
  • Catalysis
  • Cyclin C
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases*
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Cysteine Endopeptidases / metabolism
  • Drug Stability
  • Gene Expression Regulation
  • Half-Life
  • HeLa Cells
  • Humans
  • Mice
  • Multienzyme Complexes / metabolism
  • Phosphorylation
  • Proteasome Endopeptidase Complex
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Ubiquitins / metabolism

Substances

  • CCNC protein, human
  • Ccnc protein, mouse
  • Cyclin C
  • Cyclins
  • Multienzyme Complexes
  • Ubiquitins
  • Protein Serine-Threonine Kinases
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex