The orphan nuclear receptor DAX-1 acts as a novel transcriptional corepressor of PPARgamma.
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.
Kim
Gwang Sik
GS
Hormone Research Center, School of Biological Science and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Lee
Gha Young
GY
Nedumaran
Balachandar
B
Park
Yun-Yong
YY
Kim
Kyung Tae
KT
Park
Sang Chul
SC
Lee
Young Chul
YC
Kim
Jae Bum
JB
Choi
Hueng-Sik
HS
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors