Abstract
Steroid hormone receptors (SHRs) are among the best‐characterized "client" proteins of Hsp90 complexes. However, effects of Hsp90 and its co‐chaperone on SHR signal transduction have not been examined in a common system. We used a yeast system engineered to express human androgen, estrogen αand ?, glucocorticoid, mineralocorticoid, or progesterone receptors along with relevant reporter genes and tested whether Hsp90 isoproteins and p23 affected SHR signaling. Deletion of the endogenous HSC82 (homolog of human Hsp90 ?) or SBA1 (homolog of human p23) genes in this system strongly inhibited ligand‐mediated signaling of all SHRs in reporter gene assays. HSC82 gene deletion had greater impact on SHR signaling than did SBA1 gene deletions. Deletion of the HSP82 gene (homolog of human Hsp90α) did not affect SHR signaling, suggesting that the Hsc82p‐Sba1p complex specifically supports SHR signaling in this system. Effects of a lack of Hsc82p or Sba1p were restricted to SHR signaling because both cell growth and signaling by an unrelated reporter construct were unaffected by chaperone status. Geldanamycin and radicicol (Hsp90 inhibitors) strongly reduced SHR signaling at doses that did not affect cell growth. Collectively these results indicate that all SHRs, including estrogen receptorβ, are dependent on the Hsp90 chaperone system for proper function. Funded by NCI 1R33CA101622‐01A2.
Published Version
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