DAX-1 and Steroid Receptor RNA Activator (SRA) Function as Transcriptional Coactivators for Steroidogenic Factor-1 in Steroidogenesis
Xu, B; Yang, WH; Gerin, I; Hu, CD; Hammer, GD; Koenig, RJ
2008-07-01
Abstract
The nuclear receptor steroidogenic factor 1 (SF-1) is essential for adrenal development and steroidogenesis. The atypical orphan nuclear receptor Dax-1 binds to SF-1 and represses SF-1 target genes. Paradoxically, however, loss-of-function mutations of Dax-1 also cause adrenal hypoplasia, suggesting that Dax-1 may function as an SF-1 coactivator under some circumstances. Indeed, we found that Dax-1 can function as a dosage-dependent SF-1 coactivator. Both SF-1 and Dax-1 bind to steroid receptor RNA activator (SRA), a coactivator that functions as an RNA. The coactivator TIF2 also associates with Dax-1 and synergistically coactivates SF-1 target gene transcription. A naturally occurring Dax-1 mutation inhibits this transactivation, and the mutant Dax-1-TIF2 complex mislocalizes in living cells. Coactivation by Dax-1 is abolished by SRA knockdown. The expression of the steroidogenic gene products steroidogenic acute regulatory protein (StAR) and melanocortin 2 receptor is reduced in adrenal Yl cells following the knockdown of endogenous SRA. Similarly, the knockdown of endogenous Dax-1 downregulates the expression of the steroidogenic gene products CYP11A1 and StAR in both H295R adrenal and MA-10 Leydig cells. These findings reveal novel functions of SRA and Dax-1 in steroidogenesis and adrenal biology. Copyright © 2009, American Society for Microbiology.Deep Blue DOI
Other DOIs
PMID
19188450
Subjects
Adrenal Cortex Amino Acid Sequence Amino Acid Substitution Animals Cell Line DAX-1 Orphan Nuclear Receptor DNA-Binding Proteins Humans Intracellular Space Male Mice Molecular Sequence Data Mutant Proteins Nuclear Receptor Coactivator 2 Phosphoproteins Promoter Regions, Genetic Protein Binding Protein Transport RNA, Long Noncoding RNA, Small Interfering RNA, Untranslated Receptors, Retinoic Acid Repressor Proteins Steroidogenic Factor 1 Steroids Testis Trans-Activators Transcription, Genetic Transcriptional Activation
Types
Presentation
Metadata
Show full item recordCollections
Showing items related by title, author, creator and subject.
-
Detlefsen, David James (1990)
-
Katira, P.; Agarwal, A.; Fischer, T.; Chen, Hsien -Yeh.; Jiang, Xuwei; Lahann, Joerg (WILEY-VCH Verlag, 2007-10-19)
-
Scott, Jamie K.; Huang, Shan‐fu; Gangadhar, Beechanahalli P.; Samoriski, Gary M.; Clapp, Peter; Gross, Robert A.; Taussig, Ronald; Smrcka, Alan V. (John Wiley & Sons, Ltd, 2001-02-15)
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.