THE HORMONE-BINDING DOMAIN OF THE MINERALOCORTICOID RECEPTOR CAN REGULATE HETEROLOGOUS ACTIVITIES IN CIS

Steroid receptors are maintained inactive in the absence of cognate li gand partly because of repression by their hormone binding domain (HBD ). Proteins complexed with the unliganded HBD of vertebrate steroid re ceptors, including the heat-shock protein 90, have been implicated as components of a molecular switch. As such, the HBDs of both the glucoc orticoid and estrogen receptors have been shown to be autonomous regul atory cassettes which can subject heterologous activities resident on the same polypeptide to hormonal control. We show that the HBD of the mineralocorticoid receptor (MR) carries a similar ''protein inactivati on'' function. Thus, the MR HBD can be used as a movable regulatory do main, a powerful tool for aldosterone regulation of chimeric proteins. (C) 1994 Academic Press, Inc.