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http://dx.doi.org/10.14348/molcells.2020.0143

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

Kim, Sumi (Department of Microbiology and Molecular Biology, Chungnam National University)
Lee, Nari (Department of Microbiology and Molecular Biology, Chungnam National University)
Park, Eui-Soon (Department of Microbiology and Molecular Biology, Chungnam National University)
Yun, Hyeongseok (Department of Microbiology and Molecular Biology, Chungnam National University)
Ha, Tae-Uk (Department of Microbiology and Molecular Biology, Chungnam National University)
Jeon, Hyoeun (Department of Microbiology and Molecular Biology, Chungnam National University)
Yu, Jiyeon (Department of Microbiology and Molecular Biology, Chungnam National University)
Choi, Seunga (Department of Microbiology and Molecular Biology, Chungnam National University)
Shin, Bongjin (Department of Microbiology and Molecular Biology, Chungnam National University)
Yu, Jungeun (Department of Microbiology and Molecular Biology, Chungnam National University)
Rhee, Sang Dal (Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology)
Choi, Yongwon (Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine)
Rho, Jaerang (Department of Microbiology and Molecular Biology, Chungnam National University)
Publication Information
Molecules and Cells / v.44, no.1, 2021 , pp. 1-12 More about this Journal
Abstract
The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator in adipogenesis. PPARγ forms a heterodimer with another nuclear receptor, retinoid X receptor (RXR), to form an active transcriptional complex, and their transcriptional activity is tightly regulated by the association with either coactivators or corepressors. In this study, we identified T-cell death-associated gene 51 (TDAG51) as a novel corepressor of PPARγ-mediated transcriptional regulation. We showed that TDAG51 expression is abundantly maintained in the early stage of adipogenic differentiation. Forced expression of TDAG51 inhibited adipocyte differentiation in 3T3-L1 cells. We found that TDAG51 physically interacts with PPARγ in a ligand-independent manner. In deletion mutant analyses, large portions of the TDAG51 domains, including the pleckstrin homology-like, glutamine repeat and proline-glutamine repeat domains but not the proline-histidine repeat domain, are involved in the interaction with the region between residues 140 and 506, including the DNA binding domain, hinge, ligand binding domain and activation function-2 domain, in PPARγ. The heterodimer formation of PPARγ-RXRα was competitively inhibited in a ligand-independent manner by TDAG51 binding to PPARγ. Thus, our data suggest that TDAG51, which could determine adipogenic cell fate, acts as a novel negative regulator of PPARγ by blocking RXRα recruitment to the PPARγ-RXRα heterodimer complex in adipogenesis.
Keywords
adipocyte differentiation; adipogenesis; pleckstrin homology-like domain A family; peroxisome proliferator-activated receptor gamma; retinoid X receptor alpha; T-cell death-associated gene 51;
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