The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ

eLife

Hidehisa Takahashi¹  Masanobu Suzuki¹  Shigetsugu Hatakeyama¹  Wataru Mizushima¹  Masashi Watanabe¹  Takashi Ozaki¹  Shihori Itoh¹  Yasushi Saeki²  Keiji Tanaka² 

[1] Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan;Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;

关键词: TRIM23;    ubiquitin;    PPARγ;    adipocyte;    transcription;   

DOI  :  10.7554/eLife.05615

来源: DOAJ

【 摘 要 】

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. PPARγ is one of the late adipogenic activators and is known as a master regulator of adipogenesis. However, the factors that regulate PPARγ expression remain to be elucidated. Here, we show that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPARγ protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPARγ 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 PPARγ protein possibly via atypical polyubiquitin conjugation.

【 授权许可】

Unknown