Regulation of stability of cyclin-dependent kinase CDK11p110 and a caspase-processed form, CDK11p46, by Hsp90

The Biochemical Journal
Monika Mikolajczyk, Mark A Nelson

Abstract

CDK11p110 (cyclin-dependent kinase 11p110, formerly known as PITSLRE) is a member of the CDK superfamily. It associates with cyclin L and is involved in the regulation of transcription and in premRNA splicing. During staurosporine-, Fas- and tumour necrosis factor a-induced apoptosis, CDK11p110, is cleaved by caspases to generate smaller 46-50 kDa proteins containing the catalytic kinase domain. Ectopic expression of the caspase-processed form CDK11p46 induces apoptosis. The mechanisms that regulate activation and stability of CDK11 isoforms are still unclear. In the present study, we demonstrate that in human melanoma cells CDK11p110 and CDK11p46 interact with Hsp90 (heat-shock protein 90) and its co-chaperone cdc37. Furthermore, we show that the treatment of cells with the Hsp90-specific inhibitor geldanamycin leads to ubiquitination and enhanced degradation of both CDK11p110 and CDK11p46 through a proteasome-dependent pathway. We also determined that geldanamycin-triggered degradation of CDK11p46 slows down the progression of apoptosis. These results indicate that Hsp90 and cdc37 stabilize CDK11 kinase, and suggest that this stabilization is crucial for its pro-apoptotic function.

References

Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·B A BunnellV J Kidd
Jan 1, 1995·Molecular and Cellular Biology·J M LahtiV J Kidd
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·L WhitesellL M Neckers
Sep 6, 1996·The Journal of Biological Chemistry·K DaiD Beach
Apr 24, 1997·Oncogene·L LamphereJ Gyuris
Dec 19, 1998·The EMBO Journal·A Ciechanover
Feb 12, 1999·Cancer Genetics and Cytogenetics·B J DaveW G Sanger
Feb 18, 1999·Molecular and Cellular Biology·N GrammatikakisB H Cochran
Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SatoT Tsuruo
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·A ChadliD O Toft
Jan 10, 2002·The Journal of Biological Chemistry·Naoya FujitaTakashi Tsuruo
Feb 28, 2002·Molecular Cell·Guoqing ChenDavid V Goeddel
May 1, 2002·The Journal of Biological Chemistry·Liliane A DickinsonJoel M Gottesfeld
Jun 26, 2002·The Journal of Biological Chemistry·Songwen ZhangJianxin Gu
Dec 20, 2002·The Biochemical Journal·Jérôme BoudeauDario R Alessi
Feb 4, 2003·Experimental Biology and Medicine·William B Pratt, David O Toft
Feb 18, 2003·Molecular and Cellular Biology·J Alan DiehlAndrew Emili
Dec 4, 2003·Biochimica Et Biophysica Acta·Nancy A Sachs, Richard R Vaillancourt

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Citations

Mar 27, 2007·Journal of Biomedical Science·Woan-Yuh Tarn
Aug 26, 2009·Free Radical Biology & Medicine·Christina B ClarkEvelyne Gozal
Oct 29, 2014·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Yong FengZhenfeng Duan
Aug 31, 2018·International Journal of Molecular Sciences·Abdullah HoterHassan Y Naim
Jan 24, 2019·Molecular Pharmacology·John M Streicher
Oct 16, 2019·Journal of Cellular Physiology·Jianyi DingYing Jin
Jul 12, 2005·The Biochemical Journal·Yongmei FengMark A Nelson
Jan 22, 2005·Current Opinion in Genetics & Development·Laurence H Pearl
Jul 26, 2005·Biochemical and Biophysical Research Communications·Jiaqi Shi, Mark A Nelson
May 11, 2005·Biochemical and Biophysical Research Communications·Yongmei FengMark A Nelson

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