ArticleMolecular endocrinology (Baltimore, Md.)2008
DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) selectively inhibits transactivation but not transrepression mediated by the glucocorticoid receptor in a LXXLL-dependent manner.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1.Development (Cambridge, England) · 2017Article
- Compound A influences gene regulation of the Dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment.Scientific reports · 2017Article
- Cross-talk between the glucocorticoid receptor and MyoD family inhibitor domain-containing protein provides a new mechanism for generating tissue-specific responses to glucocorticoids.The Journal of biological chemistry · 2017Article
- Proteome-scale Binary Interactomics in Human Cells.Molecular & cellular proteomics : MCP · 2016Article
- The Interactome of the Glucocorticoid Receptor and Its Influence on the Actions of Glucocorticoids in Combatting Inflammatory and Infectious Diseases.Microbiology and molecular biology reviews : MMBR · 2016Review
- Clinical and molecular genetic analysis of a Chinese family with congenital X-linked adrenal hypoplasia caused by novel mutation 1268delA in the DAX-1 gene.Journal of Zhejiang University. Science. B · 2015Article
- Minireview: role of orphan nuclear receptors in cancer and potential as drug targets.Molecular endocrinology (Baltimore, Md.) · 2014Review
- The orphan nuclear receptor DAX-1 functions as a potent corepressor of the constitutive androstane receptor (NR1I3).Molecular pharmacology · 2012Article
- In vivo and in vitro evidence that PPARγ ligands are antagonists of leptin signaling in breast cancer.The American journal of pathology · 2011Article
- Orphan nuclear receptors as targets for drug development.Pharmaceutical research · 2010Review
- Hormone binding and co-regulator binding to the glucocorticoid receptor are allosterically coupled.The Journal of biological chemistry · 2010Article
- Orphan nuclear receptor DAX-1 acts as a novel corepressor of liver X receptor alpha and inhibits hepatic lipogenesis.The Journal of biological chemistry · 2010Article
- Liganded RARalpha and RARgamma interact with but are repressed by TNIP1.Biochemical and biophysical research communications · 2009Article
- Minireview: latest perspectives on antiinflammatory actions of glucocorticoids.Molecular endocrinology (Baltimore, Md.) · 2009Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The glucocorticoid receptor (GR) mediates virtually all actions of glucocorticoids, and the nature and magnitude of a cell's response to these steroids are determined primarily by hormone concentration and GR signaling capacity. DAX-1 (dosagesensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) is an orphan nuclear receptor that functions as a corepressor, and deletion or mutation of DAX-1 causes a decrease in glucocorticoid production. However it is unclear whether DAX-1 also alters GR function as a transcription factor. Here, we demonstrate that DAX-1 acts as a novel selective GR modulator. It specifically inhibits ligand-dependent GR transactivation with little effect on GR-mediated transrepression. As demonstrated by coimmunoprecipitation and glutathione- S-transferase pull-down assays, DAX-1 physically interacts with GR, but this interaction does not influence either ligand-induced GR nuclear translocation or subsequent GR association with glucocorticoid-responsive elements. Instead, DAX-1 competes with coactivators such as GR-interacting protein 1 for binding to the receptor. Specifically, suppression of GR transactivation is mediated by the N-terminal half of DAX-1, and in particular the LXXLL motifs. Thus we demonstrate that DAX-1 directly modulates GR signaling in addition to affecting glucocorticoid hormone levels.
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