Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome

EMBO J. 2003 Mar 17;22(6):1302-12. doi: 10.1093/emboj/cdg127.

Abstract

The COP9 signalosome (CSN) purified from human erythrocytes possesses kinase activity that phosphoryl ates proteins such as c-Jun and p53 with consequence for their ubiquitin (Ub)-dependent degradation. Here we show that protein kinase CK2 (CK2) and protein kinase D (PKD) co-purify with CSN. Immunoprecipitation and far-western blots reveal that CK2 and PKD are in fact associated with CSN. As indicated by electron microscopy with gold-labeled ATP, at least 10% of CSN particles are associated with kinases. Kinase activity, most likely due to CK2 and PKD, co-immuno precipitates with CSN from HeLa cells. CK2 binds to DeltaCSN3(111-403) and CSN7, whereas PKD interacts with full-length CSN3. CK2 phosphorylates CSN2 and CSN7, and PKD modifies CSN7. Both CK2 and PKD phosphorylate c-Jun as well as p53. CK2 phosphoryl ates Thr155, which targets p53 to degradation by the Ub system. Curcumin, emodin, DRB and resveratrol block CSN-associated kinases and induce degradation of c-Jun in HeLa cells. Curcumin treatment results in elevated amounts of c-Jun-Ub conjugates. We conclude that CK2 and PKD are recruited by CSN in order to regulate Ub conjugate formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • COP9 Signalosome Complex
  • Casein Kinase II
  • Curcumin / pharmacology
  • DNA-Binding Proteins
  • Dichlororibofuranosylbenzimidazole / pharmacology
  • Emodin / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Erythrocytes / chemistry
  • HeLa Cells
  • Humans
  • Multiprotein Complexes
  • Peptide Hydrolases
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / isolation & purification
  • Protein Kinase C / metabolism*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / isolation & purification
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Subunits
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteins / ultrastructure
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Resveratrol
  • Signal Transduction*
  • Stilbenes / pharmacology
  • Substrate Specificity
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitins / metabolism

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Multiprotein Complexes
  • Protein Subunits
  • Proteins
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Stilbenes
  • Tumor Suppressor Protein p53
  • Ubiquitins
  • Dichlororibofuranosylbenzimidazole
  • Adenosine Triphosphate
  • protein kinase D
  • Casein Kinase II
  • Protein Serine-Threonine Kinases
  • Protein Kinase C
  • Peptide Hydrolases
  • COP9 Signalosome Complex
  • Curcumin
  • Emodin
  • Resveratrol