title: The Mr approximately 90,000 heat shock protein: an important modulator of ligand and DNA-binding properties of the glucocorticoid receptor.
abstract: This brief report deals with some recent observations relating to the assoclation of the Mr approximately 90,000 heat shock protein (hsp90) with the glucocorticoid receptor. In its nonactivated state, stabilized by sodium molybdate, the glucocorticoid receptor exists as a 9S heteromeric complex containing a single Mr approximately 94,000 steroid-binding unit and a dimer of hsp90. Monospecific antibodies raised against the purified rat glucocorticoid receptor-associated hsp90 interact with the molybdate-stabilized receptor. They also immunoprecipitate the Mr approximately 27,000 steroid-binding fragment of the receptor generated by trypsin treatment. Thus, hsp90 interacts with the ligand-binding domain of the glucocorticoid receptor. Furthermore, dissociation of the glucocorticoid receptor-hsp90 complex results in a major reduction of the affinity of the Mr approximately 94,000 receptor entity for its ligand. The heteromeric 9S complex does not bind to DNA. When it is activated to a DNA-binding state, the hsp90 dissociates from the ligand-binding protein. In vitro, activation of the cytosolic rat glucocorticoid receptor to a DNA-binding state is inducible by the binding of ligand. Taken together, our observations indicate the existence of important connections between the association of hsp90 and the functions of ligand- and DNA-binding of the glucocorticoid receptor.
authors.affiliation: Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Denis
authors.forename: J A
authors.initials: JA
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008970:Molecular Weight; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D008024:Ligands; D011965:Receptors, Glucocorticoid; D004247:DNA