Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity
| Autor: | Marc Piechaczyk, Jacques Piette, Caroline Barette, Isabelle Jariel-Encontre |
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| Přispěvatelé: | Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Proteasome Endopeptidase Complex Cyclin E Cyclin D Cyclin A Protein Serine-Threonine Kinases Catalysis 03 medical and health sciences Mice 0302 clinical medicine Cyclin D1 Drug Stability Cyclin-dependent kinase Cyclin C Multienzyme Complexes Cyclins Genetics Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Phosphorylation Molecular Biology Ubiquitins 030304 developmental biology 0303 health sciences Cyclin-dependent kinase 1 biology 3T3 Cells Cyclin-Dependent Kinase 8 Molecular biology Cyclin-Dependent Kinases Cysteine Endopeptidases 3T3 Cells Animals COS Cells Catalysis *Cyclin-Dependent Kinases Cyclins/biosynthesis/genetics/*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/genetics/*metabolism Ubiquitins/metabolism Gene Expression Regulation COS Cells biology.protein Cyclin-dependent kinase complex 030217 neurology & neurosurgery Cyclin A2 Half-Life HeLa Cells |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2001, 20 (5), pp.551--62. ⟨10.1038/sj.onc.1204129⟩ Oncogene, 2001, 20 (5), pp.551--62. ⟨10.1038/sj.onc.1204129⟩ |
| ISSN: | 0950-9232 1476-5594 |
| DOI: | 10.1038/sj.onc.1204129⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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