Evidence that removal of an endogenous metal that stabilizes the untransformed glucocorticoid receptor in cytosol allows ligand-independent receptor transformation.
Cytosol preparations contain an endogenous heat-stable factor which stabilizes the glucocorticoid receptor in its untransformed, non DNA-binding form. Elution of a partially purified preparation of this stabilizing factor through a metal chelating resin (Chelex-100) leads to the loss of its ability to inhibit temperature-mediated transformation of the receptor. Sodium molybdate mimicks the ability of this endogenous metal to stabilize the untransformed receptor, and it too is adsorbed by Chelex resin. When an L-cell cytosol preparation containing the glucocorticoid receptor is passed through a column of Chelex-100 resin and then incubated at 15 degrees C, the receptor is rapidly transformed to the DNA-binding state, regardless of whether it is steroid-bound or not. In contrast, whole cytosol containing endogenous metals is transformed to the DNA-binding state only when the receptor is both steroid-bound and exposed to elevated temperature. these data suggest that a metal (or metals) may be involved in conferring the property of ligand-dependency to the transformation process.
Meshinchi
S
S
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Pratt
W B
WB
D000818:Animals; D002846:Chromatography, Affinity; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D007700:Kinetics; D007739:L Cells / Q000378:metabolism; D008024:Ligands; D008670:Metals / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008982:Molybdenum / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*
D008024:Ligands; D008670:Metals; D011965:Receptors, Glucocorticoid; C044659:molybdate; D008982:Molybdenum; D004247:DNA