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Exp Mol Med. 2018 Oct 15;50(10):135. doi: 10.1038/s12276-018-0162-6.

The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasome-mediated degradation of PPARγ.

Author information

1
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea.
2
Center for Genomic Integrity (CGI), Institute for Basic Science (IBS), Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea.
3
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea. janghchoi@unist.ac.kr.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPARγ is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPARγ, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPARγ, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPARγ. The stable expression of TRIM25 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPARγ 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 PPARγ and that TRIM25 is a novel target for PPARγ-associated metabolic diseases.

PMID:
30323259
PMCID:
PMC6189217
DOI:
10.1038/s12276-018-0162-6
[Indexed for MEDLINE]
Free PMC Article

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