The role of N-terminal domain in regulation of mineralocorticoid receptor function

Abstract

The N-terminal domain of the mineralocorticoid receptor (MR) exhibits no significant sequence homology to the highly related glucocorticoid receptor. I report here that amino acids 450--602 of the N-terminus play a role in three aspects of MR degradation: (1) degradation in the absence of aldosterone mediated by the 26S proteasome, (2) degradation in the presence of aldosterone mediated by the 26S proteasome, and (3) degradation in the presence of aldosterone not mediated by the 26S proteasome. Concurrently I determined that aldosterone treatment following transient expression of MR in Cos-7 cells induced the appearance of higher molecular weight forms of the receptor. I determined that two regions within the N-terminus of MR were required for the appearance of the aldosterone-stimulated shift in molecular weight. Furthermore, the type of agonist, nuclear occupancy and the cell type employed influenced the shift in molecular weight of MR.