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| Subject Categories: Signal Transduction | Proteins |
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| The EMBO Journal
(2003) 22, 1302–1312, doi:10.1093/emboj/cdg127 |
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| Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome |
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| Stefan Uhle1, Ohad Medalia2, Richard Waldron3, Renate Dumdey1, Peter Henklein4, Dawadschargal Bech-Otschir1, Xiaohua Huang1, Matthias Berse1, Joseph Sperling5, Rüdiger Schade6 and Wolfgang Dubiel1 |
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1 Division of Molecular Biology, Department of Surgery, Humboldt University, Monbijoustrasse 2, D-10117 Berlin, Germany 2 Department of Structural Biology, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany 3 Department of Medicine, Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, CA 90095-1786, USA 4 Institute of Biochemistry, , Humboldt University, Monbijoustrasse 2, D-10117 Berlin, Germany 5 Department of Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel 6 Institute of Pharmacology and Toxicology, Medical Faculty Charité, Humboldt University, Monbijoustrasse 2, D-10117 Berlin Germany To whom correspondence should be addressed Wolfgang Dubiel, wolfgang.dubiel@charite.de Received 20 June 2002; Revised 22 November 2002; Accepted 20 January 2003. |
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| Abstract |
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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  CSN3(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. |
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| Keywords: c-Jun, COP9 signalosome, protein kinase CK2, protein kinase D, p53 |
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