Departments of bPharmacology and

It is now well established that steroid receptors in hormone-free cells are associated with the 90-kDa heat shock protein, hsp90 (for review, see Pratt1s2). The receptor-heat shock protein interaction has been most extensively studied for glucocorticoid receptors (GR) and progesterone receptors (PR). In both cases it has been shown that hsp90 interacts with the hormone binding domain (HBD), = and that binding of steroid to the HBD promotes dissociation of the receptor from h ~ p 9 0. ~ From the study of mutant receptors it is clear that the HBD performs at least three functions required for hormonal regulation of receptor function: (1) It represses the transcrip-tional activating activity of the receptor, (2) it binds hormone, and (3) it determines hormone-regulated derepression of receptor f u n c t i ~ n. ~. ~ The inactivating function of the HBD can be conferred to fusion proteins, bringing their activity under hormonal c o n t r ~ l. ~ J ~ Recently we have used some fusion proteins containing P-galactosidase and portions of the rat GRl1 to demonstrate that the GR HBD is sufficient to confer hormonally regulated binding of fusion protein to h ~ p 9 0. l ~ Taken together with earlier reports demonstrating a correlation between hormone-regulated transcrip