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

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860201
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Hokkaido University
• Principal Investigator: WATANABE masashi 北海道大学, 医学(系)研究科(研究院), 助教 (10632424)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ユビキチン / PPARガンマー / ユビキチンリガーゼ

Outline of Final Research Achievements

Adipocyte differentiation is a tightly controlled process regulated by complex transcriptional activators. Multiple adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by the late adipogenic activators, which coordinate the formation of late enhanceosomes. PPARgamma is one of the late adipogenic activators and is considered the master regulator of adipogenesis. We showed that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPARgamma protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPARgamma protein abundance during preadipocyte differentiation, resulting in a severe defect in late adipogenic differentiation, whereas it did not affect the formation of early enhanceosomes. This adipogenic defect is rescued by ectopic expression of PPARgamma.

Free Research Field

医化学一般