Journal article
The N-terminal domain of the mineralocorticoid receptor modulates both mineralocorticoid receptor- and glucocorticoid receptor-mediated transactivation from Na/K ATPase beta1 target gene promoter
Endocrine, v 13(3), pp 287-295
01 Dec 2000
PMID: 11216640
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mineralocorticoid and glucocorticoid hormones activate the expression of the Na/K ATPase beta1 through direct binding of the mineralocorticoid receptor (MR) and glucocorticoid receptors (GR) to a mineralocorticoid- and glucocorticoid-responsive element in the beta1 promoter region, but activation of the beta1 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 beta1 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 beta1 gene promoter.
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Details
- Title
- The N-terminal domain of the mineralocorticoid receptor modulates both mineralocorticoid receptor- and glucocorticoid receptor-mediated transactivation from Na/K ATPase beta1 target gene promoter
- Creators
- A DerfoulN M RobertsonD J HallG Litwack
- Publication Details
- Endocrine, v 13(3), pp 287-295
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- SOM Dean - Research Administration
- Web of Science ID
- WOS:000166655500008
- Scopus ID
- 2-s2.0-0034490057
- Other Identifier
- 991021463534104721
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- Web of Science research areas
- Endocrinology & Metabolism