The N-terminal domain of the mineralocorticoid receptor modulates both mineralocorticoid receptor-and glucocorticoid receptor-mediated transactivation from Na/K ATPase β1 target gene promoter

Author： Derfoul Assia Robertson Noreen Hall David Litwack Gerald

Publisher： Humana Press, Inc

ISSN： 0969-711X

Source： Endocrine Journal, Vol.13, Iss.3, 2000-12, pp. : 287-295

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Mineralocorticoid and glucocorticoid hormones activate the expression of the Na/K ATPase β1 through direct binding of the mineralocorticoid receptor (MR) and glucocorticoid receptors (GR) to a mineralocorticoid-and glucocorticoid-responsive element in the β1 promoter region, but activation of the β1 promoter is inhibited by coexpression of both receptors. Here, using a series of mutated and chimeric receptors, we show that the N-terminal region of MR mediates an inhibitory effect on MR and GR activation from the β1 promoter, in CV-1 cells. Deletion of the N-terminal region of MR (1-603) enhanced MR activation four-fold. Activation by chimeric MR, in which the N-terminus of GR replaces the N-terminal region of MR, was threefold that of wild-type MR. In addition, whereas coexpression of wild-type MR and GR was inhibitory, coexpression of chimeric MR and wild-type GR was nearly equal to that of MR. By contrast, mutated GR lacking its N-terminal region (1–420) was less efficient than the wild type in activating this promoter. These results demonstrate that the N-terminal domains of MR and GR have opposite transactivation properties and that MR region 1–603 is indeed inhibitory for both MR- and GR-mediated regulation of the Na/K ATPase β1 gene promoter.