title: Role of molecular chaperones in steroid receptor action.
abstract: Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.
authors.affiliation: Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI 48109, U.S.A. annat@umich.edu
authors.forename: William B
authors.initials: WB
authors.lastname: Pratt
authors.forename: Mario D
authors.initials: MD
authors.lastname: Galigniana
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Morishima
authors.forename: Patrick J M
authors.initials: PJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid