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

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.
Mesh Terms:
Adenosine Triphosphate, Casein Kinase II, Curcumin, DNA-Binding Proteins, Dichlororibofuranosylbenzimidazole, Emodin, Enzyme Inhibitors, Erythrocytes, HeLa Cells, Humans, Multiprotein Complexes, Peptide Hydrolases, Phosphorylation, Protein Kinase C, Protein Subunits, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins c-jun, Recombinant Proteins, Signal Transduction, Stilbenes, Substrate Specificity, Tumor Suppressor Protein p53, Ubiquitins
EMBO J.
Date: Mar. 17, 2003
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