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KMID : 0578320210440010001
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Molecules and Cells
2021 Volume.44 No. 1 p.1 ~ p.12
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T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγRXRα Heterodimer Formation in Adipogenesis
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Kim Su-Mi
Lee Na-Ri
Park Eui-Soon
Yun Hyeong-Seok
Ha Tae-Uk
Jeon Hyo-Eun
Yu Ji-Yeon
Choi Seung-A
Shin Bong-Jin
Yu Jung-Eun
Rhee Sang-Dal
Choi Yong-Won
Rho Jae-Rang
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Abstract
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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.
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KEYWORD
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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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