The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPAR?.

ABSTRACT: Adipocyte differentiation is a strictly controlled process regulated by a series of transcriptional activators. Adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by late enhanceosomes. PPAR? is one of the late adipogenic activators and is known as a master regulator of adipogenesis. However, the factors that regulate PPAR? expression remain to be elucidated. Here, we show that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPAR? protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPAR? protein abundance during preadipocyte differentiation, resulting in a severe defect in late adipogenic differentiation, whereas it did not affect the formation of early enhanceosomes. Our results suggest that TRIM23 plays a critical role in the switching from early to late adipogenic enhanceosomes by stabilizing PPAR? protein possibly via atypical polyubiquitin conjugation.

SUBMITTER: Watanabe M 

PROVIDER: S-EPMC4426667 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature