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

• Published in: The EMBO journal Vol. 22; no. 6; pp. 1302 - 1312
• Main Authors: Uhle, Stefan, Medalia, Ohad, Waldron, Richard, Dumdey, Renate, Henklein, Peter, Bech-Otschir, Dawadschargal, Huang, Xiaohua, Berse, Matthias, Sperling, Joseph, Schade, Rüdiger, Dubiel, Wolfgang
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 17.03.2003; Blackwell Publishing Ltd; Oxford University Press
• Subjects: Adenosine Triphosphate - metabolism; c-Jun; Casein Kinase II; COP9 signalosome; COP9 Signalosome Complex; Curcumin - pharmacology; Dichlororibofuranosylbenzimidazole - pharmacology; DNA-Binding Proteins; Emodin - pharmacology; Enzyme Inhibitors - pharmacology; Erythrocytes - chemistry; HeLa Cells; Humans; Multiprotein Complexes; p53; Peptide Hydrolases; Phosphorylation; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - isolation & purification; Protein Kinase C - metabolism; protein kinase CK2; protein kinase D; Protein Subunits; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - isolation & purification; Protein-Serine-Threonine Kinases - metabolism; 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; Signal Transduction; Stilbenes - pharmacology; Substrate Specificity; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Ubiquitins - metabolism
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdg127

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. Immunoprecipi tation 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 ΔCSN3(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.