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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
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
2008-04-03
Publisher
Elsevier
Citation
Biochemical and Biophysical Research Communications 370 (2008) 264-268
Keywords
3T3-L1 CellsAdipogenesis/*geneticsAnimalsBinding, CompetitiveCell LineDNA-Binding Proteins/genetics/*metabolism*Gene Expression RegulationHeat-Shock Proteins/antagonists & inhibitors/metabolismHumansMicePPAR gamma/*antagonists & inhibitors/metabolismReceptors, Retinoic Acid/genetics/*metabolismRepressor Proteins/genetics/*metabolismTranscription Factors/antagonists & inhibitors/metabolismTranscription, GeneticTranscriptional ActivationTransfection
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
DOI
https://doi.org/10.1016/j.bbrc.2008.03.098
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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