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  • The EMBO Journal (2003) 22, 1302 - 1312
  • doi:10.1093/emboj/cdg127

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

Stefan Uhle1, Ohad Medalia2, Richard Waldron3, Renate Dumdey1, Peter Henklein4, Dawadschargal Bech-Otschir1, Xiaohua Huang1, Matthias Berse1, Joseph Sperling5, Rüdiger Schade6 and Wolfgang Dubiel1

  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

Correspondence to:

Wolfgang Dubiel, E-mail: wolfgang.dubiel@charite.de

Received 20 June 2002; Accepted 20 January 2003; Revised 22 November 2002

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 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.

  • Keywords:

    • c-Jun,
    • COP9 signalosome,
    • protein kinase CK2,
    • protein kinase D,
    • p53