T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγRXRα Heterodimer Formation in Adipogenesis

摘要: The nuclear receptor peroxisome proliferator-activated γ (PPARγ) is the master transcriptional regulator in adipogenesis. PPARγ forms a heterodimer with another receptor, retinoid X (RXR), to form an active complex, and their activity tightly regulated by association either coactivators or corepressors. In this study, we identified T-cell death-associated gene 51 (TDAG51) as novel corepressor of PPARγ-mediated regulation. We showed that TDAG51 expression abundantly maintained early stage adipogenic differentiation. Forced inhibited adipocyte differentiation 3T3-L1 cells. found physically interacts ligand-independent manner. deletion mutant analyses, large portions domains, including pleckstrin homology-like, glutamine repeat proline-glutamine domains but not proline-histidine domain, are involved interaction region between residues 140 506, DNA binding hinge, ligand domain activation function-2 PPARγ. formation PPARγ-RXRα was competitively manner Thus, our data suggest TDAG51, which could determine cell fate, acts negative blocking RXRα recruitment complex