This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chadli, A. Articles by Toft, D. Search for Related Content PubMed PubMed Citation Articles by Chadli, A. Articles by Toft, D.

GCUNC-45 Is a Novel Regulator for the Progesterone Receptor/hsp90 Chaperoning Pathway

Ahmed Chadli,^1, J. Dinny Graham,^2,, M. Greg Abel,² Twila A. Jackson,² David F. Gordon,² William M. Wood,² Sara J. Felts,¹ Kathryn B. Horwitz,² and David Toft^1*

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota,¹ Division of Endocrinology, Department of Medicine, University of Colorado Health Science Center, Denver, Colorado²

Received 13 September 2005/ Returned for modification 9 October 2005/ Accepted 19 December 2005

The hsp90 chaperoning pathway is a multiprotein system that is required for the production or activation of many cell regulatory proteins, including the progesterone receptor (PR). We report here the identity of GCUNC-45 as a novel modulator of PR chaperoning by hsp90. GCUNC-45, previously implicated in the activities of myosins, can interact in vivo and in vitro with both PR-A and PR-B and with hsp90. Overexpression and knockdown experiments show GCUNC-45 to be a positive factor in promoting PR function in the cell. GCUNC-45 binds to the ATP-binding domain of hsp90 to prevent the activation of its ATPase activity by the cochaperone Aha1. This effect limits PR chaperoning by hsp90, but this can be reversed by FKBP52, a cochaperone that is thought to act later in the pathway. These findings reveal a new cochaperone binding site near the N terminus of hsp90, add insight on the role of FKBP52, and identify GCUNC-45 as a novel regulator of the PR signaling pathway.

A.C. and J.D.G. contributed equally to this study.

Present address: Westmead Institute for Cancer Research, University of Sydney Westmead Hospital, Westmead, New South Wales, Australia.

This article has been cited by other articles:

• Liu, L., Srikakulam, R., Winkelmann, D. A. (2008). Unc45 Activates Hsp90-dependent Folding of the Myosin Motor Domain. J. Biol. Chem. 283: 13185-13193 [Abstract] [Full Text]  
• Chadli, A., Felts, S. J., Toft, D. O. (2008). GCUNC45 Is the First Hsp90 Co-chaperone to Show {alpha}/{beta} Isoform Specificity. J. Biol. Chem. 283: 9509-9512 [Abstract] [Full Text]  
• Nonclercq, D., Journe, F., Laios, I., Chaboteaux, C., Toillon, R.-A., Leclercq, G., Laurent, G. (2007). Effect of nuclear export inhibition on estrogen receptor regulation in breast cancer cells. J Mol Endocrinol 39: 105-118 [Abstract] [Full Text]  
• Cintron, N. S., Toft, D. (2006). Defining the Requirements for Hsp40 and Hsp70 in the Hsp90 Chaperone Pathway. J. Biol. Chem. 281: 26235-26244 [Abstract] [Full Text]