HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 5, 2989-2998, February 3, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/5/2989    most recent M508687200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arlander, S. J. H. Articles by Karnitz, L. M. Search for Related Content PubMed PubMed Citation Articles by Arlander, S. J. H. Articles by Karnitz, L. M. Social Bookmarking                      What's this?

Chaperoning Checkpoint Kinase 1 (Chk1), an Hsp90 Client, with Purified Chaperones^*

Sonnet J. H. Arlander, Sara J. Felts, Jill M. Wagner^¶, Bridget Stensgard, David O. Toft, and Larry M. Karnitz^¶||1

From the Departments of Molecular Pharmacology and Experimental Therapeutics and Biochemistry and Molecular Biology, Mayo Graduate School, and the ^¶Division of Developmental Oncology Research and the ^||Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Checkpoint kinase 1 (Chk1), a serine/threonine kinase that regulates DNA damage checkpoints, is destabilized when heat shock protein 90 (Hsp90) is inhibited, suggesting that Chk1 is an Hsp90 client. In the present work we examined the interplay between Chk1 and Hsp90 in intact cells, identified a source of unchaperoned Chk1, and report the in vitro chaperoning of Chk1 in reticulocyte lysates and with purified chaperones and co-chaperones. We find that bacterially expressed Chk1 is post-translationally chaperoned to an active kinase. This reaction minimally requires Hsp90, Hsp70, Hsp40, Cdc37, and the protein kinase CK2. The co-chaperone Hop, although not essential for the activation of Chk1 in vitro, enhanced the chaperoning process, whereas the co-chaperone p23 did not stimulate the chaperoning reaction. Additionally, we found that the C-terminal regulatory domain of Chk1 affects the association of Chk1 with Hsp90. Collectively these results provide new insights into Hsp90-dependent chaperoning of a client kinase and identify a novel, biochemically tractable model system that will be useful to further dissect the Hsp90-dependent chaperoning of this important and ubiquitous class of Hsp90 clients.

Received for publication, August 8, 2005 , and in revised form, November 22, 2005.

^* This work was supported in part by National Institutes of Health Grants CA104378 (to L. M. K.) and DK46249 (to D. O. T.) and a predoctoral fellowship from the Mayo Foundation (to S. J. H. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Guggenheim 13, Mayo Clinic College of Medicine, 200 First St. Southwest, Rochester, MN 55905. Tel.: 507-284-3124; Fax: 507-284-3906; E-mail: karnitz.larry{at}mayo.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Mashukova, A. S. Oriolo, F. A. Wald, M. L. Casanova, C. Kroger, T. M. Magin, M. B. Omary, and P. J. I. Salas Rescue of atypical protein kinase C in epithelia by the cytoskeleton and Hsp70 family chaperones J. Cell Sci., July 15, 2009; 122(14): 2491 - 2503. [Abstract] [Full Text] [PDF]

				S. Madlener, M. Rosner, S. Krieger, B. Giessrigl, M. Gridling, T. P. N. Vo, C. Leisser, A. Lackner, I. Raab, M. Grusch, et al. Short 42{degrees}C heat shock induces phosphorylation and degradation of Cdc25A which depends on p38MAPK, Chk2 and 14.3.3 Hum. Mol. Genet., June 1, 2009; 18(11): 1990 - 2000. [Abstract] [Full Text] [PDF]

				A. N. Tse, T. N. Sheikh, H. Alan, T.-C. Chou, and G. K. Schwartz 90-kDa Heat Shock Protein Inhibition Abrogates the Topoisomerase I Poison-Induced G2/M Checkpoint in p53-Null Tumor Cells by Depleting Chk1 and Wee1 Mol. Pharmacol., January 1, 2009; 75(1): 124 - 133. [Abstract] [Full Text] [PDF]

				A. K. Mandal, N. B. Nillegoda, J. A. Chen, and A. J. Caplan Ydj1 Protects Nascent Protein Kinases from Degradation and Controls the Rate of Their Maturation Mol. Cell. Biol., July 1, 2008; 28(13): 4434 - 4444. [Abstract] [Full Text] [PDF]

				V. L. Gabai, C. O'Callaghan-Sunol, L. Meng, M. Y. Sherman, and J. Yaglom Triggering Senescence Programs Suppresses Chk1 Kinase and Sensitizes Cells To Genotoxic Stresses Cancer Res., March 15, 2008; 68(6): 1834 - 1842. [Abstract] [Full Text] [PDF]

				T. Zhang, A. Hamza, X. Cao, B. Wang, S. Yu, C.-G. Zhan, and D. Sun A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells Mol. Cancer Ther., January 1, 2008; 7(1): 162 - 170. [Abstract] [Full Text] [PDF]

				N. Wayne and D. N. Bolon Dimerization of Hsp90 Is Required for in Vivo Function: DESIGN AND ANALYSIS OF MONOMERS AND DIMERS J. Biol. Chem., November 30, 2007; 282(48): 35386 - 35395. [Abstract] [Full Text] [PDF]

				L. M. Karnitz and S. J. Felts Cdc37 Regulation of the Kinome: When to Hold 'Em and When to Fold 'Em Sci. Signal., May 8, 2007; 2007(385): pe22 - pe22. [Abstract] [Full Text] [PDF]

				A. K. Mandal, P. Lee, J. A. Chen, N. Nillegoda, A. Heller, S. DiStasio, H. Oen, J. Victor, D. M. Nair, J. L. Brodsky, et al. Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation J. Cell Biol., January 29, 2007; 176(3): 319 - 328. [Abstract] [Full Text] [PDF]

				A. J. Bredemeyer, P. E. Carrigan, T. A. Fehniger, D. F. Smith, and T. J. Ley Hop Cleavage and Function in Granzyme B-induced Apoptosis J. Biol. Chem., December 1, 2006; 281(48): 37130 - 37141. [Abstract] [Full Text] [PDF]

				G. S. Nowakowski, A. K. McCollum, M. M. Ames, S. J. Mandrekar, J. M. Reid, A. A. Adjei, D. O. Toft, S. L. Safgren, and C. Erlichman A phase I trial of twice-weekly 17-allylamino-demethoxy-geldanamycin in patients with advanced cancer. Clin. Cancer Res., October 15, 2006; 12(20): 6087 - 6093. [Abstract] [Full Text] [PDF]