The orphan nuclear receptor DAX-1 acts as a novel transcriptional corepressor of PPAR{gamma}
- Hormone Research Center, School of Biological Science and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of)
- Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742 (Korea, Republic of)
- Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)
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 PPAR{gamma}. Transient transfection assays demonstrated that DAX-1 inhibits the transactivity of PPAR{gamma} in a dose-dependent manner. DAX-1 directly competed with the PPAR{gamma} coactivator (PGC)-1{alpha} for binding to PPAR{gamma}. 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 PPAR{gamma} target genes, resulting in an attenuation of adipogenesis in 3T3-L1 cells. Our results suggest that DAX-1 acts as a corepressor of PPAR{gamma} and performs a potential function in the regulation of PPAR{gamma}-mediated cellular differentiation.
- OSTI ID:
- 21143701
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 370, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.03.098; PII: S0006-291X(08)00546-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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