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

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPAR? 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?, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPAR?, 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?. The stable expression of TRIM25 reduced PPAR? protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPAR? 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? and that TRIM25 is a novel target for PPAR?-associated metabolic diseases.

SUBMITTER: Lee JM 

PROVIDER: S-EPMC6189217 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature