S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biochemistry & Molecular Biology (생화학교실) Journal Papers (저널논문_생화학교실)
The orphan nuclear receptor DAX-1 acts as a novel transcriptional corepressor of PPARgamma
- Kim, Gwang Sik; Lee, Gha Young; Nedumaran, Balachandar; Park, Yun-Yong; Kim, Kyung Tae; Park, Sang Chul; Lee, Young Chul; Kim, Jae Bum; Choi, Hueng-Sik
- Issue Date
- Biochemical and Biophysical Research Communications 370 (2008) 264-268
- 3T3-L1 Cells; Adipogenesis/*genetics; Animals; Binding, Competitive; Cell Line; DNA-Binding Proteins/genetics/*metabolism; *Gene Expression Regulation; 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
- 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.
- 1090-2104 (Electronic)
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