Inhibition of Glucocorticoid Receptor Conversion to the DNA-Binding State and Inhibition of Subunit Dissociation

Abstract

When steroid-bound glucocorticoid receptors present in cell-free lysates are exposed either to elevated temperatures or to increased ionic strength, they are transformed from a state that does not bind to DNA to one that does bind to DNA (1). This transformation event is accompanied by a shift in the size of the receptor from an oligomer of approximately 320,000 Da to a monomer of approximately 100,000 Da (2–4). Numerous proposals have been made to explain the oligomeric nature of the untransformed glucocorticoid receptor (see Ref. 1 for review). Among these, is the idea that the receptor oligomer is a tetramer of identical steroid-binding subunits (1). We now know, however, that the untransformed glucocorticoid receptor in mouse L-cell cytosol is a heteromer which contains a 100-kDa steroid-binding phosphoprotein and a 90-kDa non-steroid-binding phosphoprotein (5). In addition, we have used immunological techniques to show that the non-steroid-binding subunit of the L-cell receptor complex is the murine 90-kDa heat shock protein (6). These results are in agreement with those recently reported for the progesterone receptor complex in chick oviduct cytosol. The affinity purified untransformed progesterone receptor complex contains a 90-kDa phosphoprotein which does not bind progestin (7,8).