Heat shock induces translocation to the nucleus of the unliganded glucocorticoid receptor.
There have been many reports demonstrating the specific association of several heat shock proteins with unliganded steroid hormone receptors. However, little evidence to date has been proposed to link steroid receptor action with the heat shock response in cells. In this paper, we demonstrate the effect of heat and chemical stress on glucocorticoid receptor subcellular localization in mouse L929 cells and in a stably transfected Chinese hamster ovary cell line (WCL2) which over-expresses the mouse glucocorticoid receptor. When WCL2 cells are exposed to 43 degrees C, there is a time-dependent decrease in glucocorticoid receptor hormone-binding capacity in the cytosolic fraction of these cells that correlates with a decrease in amount of glucocorticoid receptor protein. Analysis of both cytosolic and nuclear fractions for glucocorticoid receptor protein via quantitative Western blotting reveals that the unliganded glucocorticoid receptor of non-shocked L929 and WCL2 cells is localized primarily in the cytosolic fraction, whereas unliganded receptor of heat-shocked cells is found almost exclusively in the nuclear fraction. A similar shift to nuclear localization for unliganded glucocorticoid receptor is noted in L929 and WCL2 cells subjected to chemical shock (sodium arsenite). As treatment of these cells with glucocorticoid hormone also results in glucocorticoid receptor that is tightly bound within the nuclear fraction, it is speculated that heat and chemical stress provide a hormone-independent mechanism by which glucocorticoid receptor is transformed to the high affinity nuclear-binding state characteristic of the hormone-bound, transcriptionally active receptor.
Sanchez
E R
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Department of Pharmacology, Medical College of Ohio, Toledo 43699.
D000818:Animals; D001151:Arsenic / Q000737:chemistry; D018053:Arsenites; D001692:Biological Transport; D015153:Blotting, Western; D002458:Cell Fractionation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008024:Ligands; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D017670:Sodium Compounds
D018053:Arsenites; D006360:Heat-Shock Proteins; D008024:Ligands; D011965:Receptors, Glucocorticoid; D017670:Sodium Compounds; C017947:sodium arsenite; D001151:Arsenic