KMID : 0620920180500100135
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Experimental & Molecular Medicine 2018 Volume.50 No. 10 p.135 ~ p.135
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The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasome-mediated degradation of PPAR¥ã
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Lee Jae-Min
Choi Sun-Sil Lee Yo-Han Khim Keon-Woo Yoon So-Ra Kim Byung-Gyu Nam Dou-Gu Suh Pann-Ghill Myung Kyung-Jae Choi Jang-Hyun
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Abstract
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Peroxisome proliferator-activated receptor gamma (PPAR¥ã) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPAR¥ã is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPAR¥ã, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPAR¥ã, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPAR¥ã. The stable expression of TRIM25 reduced PPAR¥ã protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPAR¥ã protein levels and stimulated adipocyte differentiation. Furthermore, TRIM25-knockout mouse embryonic fibroblasts (MEFs) exhibited an increased adipocyte differentiation capability compared with wild-type MEFs. Taken together, these data indicate that TRIM25 is a novel E3 ubiquitin ligase of PPAR¥ã and that TRIM25 is a novel target for PPAR¥ã-associated metabolic diseases.
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KEYWORD
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Differentiation, Ubiquitylation
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