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

Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St. Southwest, Rochester, MN 55905, USA.

Molecular and cellular biology 2006 Mar

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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.

Citation

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. GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Molecular and cellular biology. 2006 Mar;26(5):1722-30