title: The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ.
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. 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.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shihori
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizushima
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D059305:Diet, High-Fat; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D025821:Polyubiquitin / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D047495:PPAR gamma; D034741:RNA, Small Interfering; C080681:TRIM23 protein, human; D025821:Polyubiquitin; D008156:Luciferases; D019204:GTP-Binding Proteins
keywords: PPARγ; TRIM23; adipocyte; biochemistry; cell biology; human; mouse; transcription; ubiquitin