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The orphan nuclear receptor DAX-1 acts as a novel transcriptional corepressor of PPARgamma
Cited 12 time in
Web of Science
Cited 12 time in Scopus
- Authors
- Issue Date
- 2008-04-03
- Publisher
- Elsevier
- Citation
- Biochemical and Biophysical Research Communications 370 (2008) 264-268
- Keywords
- 3T3-L1 Cells ; Adipogenesis/*genetics ; Animals ; Binding, Competitive ; Cell Line ; DNA-Binding Proteins/genetics/*metabolism ; Heat-Shock Proteins/antagonists & inhibitors/metabolism ; Humans ; Mice ; PPAR gamma/*antagonists & inhibitors/metabolism ; Receptors, Retinoic Acid/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; Transcription Factors/antagonists & inhibitors/metabolism ; Transcription, Genetic ; Transcriptional Activation ; Transfection ; Gene Expression Regulation
- Abstract
- DAX-1 is an atypical nuclear receptor (NR) which functions primarily as a transcriptional corepressor of other NRs via heterodimerization. Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-dependent NR which performs a key function in adipogenesis. In this study, we evaluated a novel cross-talk mechanism between DAX-1 and PPARgamma. Transient transfection assays demonstrated that DAX-1 inhibits the transactivity of PPARgamma in a dose-dependent manner. DAX-1 directly competed with the PPARgamma coactivator (PGC)-1alpha for binding to PPARgamma. Endogenous levels of DAX-1 were significantly lower in differentiated 3T3-L1 adipocytes as compared to preadipocytes. Using a retroviral expression system, we demonstrated that DAX-1 overexpression downregulates the expression of PPARgamma target genes, resulting in an attenuation of adipogenesis in 3T3-L1 cells. Our results suggest that DAX-1 acts as a corepressor of PPARgamma and performs a potential function in the regulation of PPARgamma-mediated cellular differentiation.
- ISSN
- 1090-2104 (Electronic)
- Language
- English
- URI
- http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4S5V130-3-B&_cdi=6713&_user=168665&_orig=search&_coverDate=05%2F30%2F2008&_sk=996299997&view=c&wchp=dGLbVlz-zSkWA&md5=bb9ac079743a71a2e45962a8da053115&ie=/sdarticle.pdf
https://hdl.handle.net/10371/67487
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