DAX-1 and Steroid Receptor RNA Activator (SRA) Function as Transcriptional Coactivators for Steroidogenic Factor-1 in Steroidogenesis

التفاصيل البيبلوغرافية
العنوان: DAX-1 and Steroid Receptor RNA Activator (SRA) Function as Transcriptional Coactivators for Steroidogenic Factor-1 in Steroidogenesis
المؤلفون: Xu, B, Yang, WH, Gerin, I, Hu, CD, Hammer, GD, Koenig, RJ
سنة النشر: 2023
المجموعة: University of Michigan: Deep Blue
مصطلحات موضوعية: 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, Small Interfering, Untranslated, Receptors, Retinoic Acid, Repressor Proteins, Steroidogenic Factor 1, Steroids, Testis, Trans-Activators
جغرافية الموضوع: Qingdao, China
الوصف: 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. ; Experimental Marine Biological Laboratory, Institute of Oceanology, Academia Sinica ; http://deepblue.lib.umich.edu/bitstream/2027.42/191162/2/XuTest et al., Dax-1 JCB 2009 1010-08.pdf ; Description of Xu et al., Dax-1 JCB 2009 1010-08.pdf : Published version
نوع الوثيقة: conference object
وصف الملف: application/pdf
اللغة: English
العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/19188450Test; https://hdl.handle.net/2027.42/191162Test; https://dx.doi.org/10.7302/21551Test; orcid:0000-0001-7429-3908; orcid:0000-0001-6843-3628; orcid:0000-0003-0021-4976; Xu, B; 0000-0001-7429-3908; Yang, WH; Gerin, I; Hu, CD; Hammer, GD; 0000-0001-6843-3628; Koenig, RJ; 0000-0003-0021-4976
DOI: 10.1128/MCB.01010-08
DOI: 10.7302/21551
الإتاحة: https://doi.org/10.1128/MCB.01010-08Test
https://doi.org/10.7302/21551Test
https://hdl.handle.net/2027.42/191162Test
https://www.ncbi.nlm.nih.gov/pubmed/19188450Test
رقم الانضمام: edsbas.B5B33820
قاعدة البيانات: BASE