GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway

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

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47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1722-1730
Number of pages9
JournalMolecular and Cellular Biology
Volume26
Issue number5
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Chadli, A., Graham, J. D., Abel, M. G., Jackson, T. A., Gordon, D. F., Wood, W. M., ... Toft, D. (2006). GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Molecular and Cellular Biology, 26(5), 1722-1730. https://doi.org/10.1128/MCB.26.5.1722-1730.2006