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.
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Derfoul, A., Robertson, N.M., Hall, D.J. et al. 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. Endocr 13, 287–295 (2000). https://doi.org/10.1385/ENDO:13:3:287
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DOI: https://doi.org/10.1385/ENDO:13:3:287