The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex

被引：32

作者：

Zhang, Wenxiang ^{[1
]}

Xu, Jinjin ^{[1
]}

Li, Jinhui ^{[1
]}

Guo, Tong ^{[1
]}

Jiang, Dan ^{[2
]}

Feng, Xue ^{[1
]}

Ma, Xueyan ^{[1
]}

He, Lingli ^{[1
]}

Wu, Wenqing ^{[1
]}

Yin, Mengxin ^{[1
]}

Ge, Ling ^{[1
]}

Wang, Zuoyun ^{[1
]}

Ho, Margaret S. ^{[2
]}

Zhao, Yun ^{[1
,2
]}

Fei, Zhaoliang ^{[1
]}

Zhang, Lei ^{[1
,2
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol,Innovat Ctr Cel, State Key Lab Cell Biol,Chinese Acad Sci Ctr Exce, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2018年 / 293卷 / 44期

基金：

中国国家自然科学基金;

关键词：

adipogenesis; Hippo pathway; Yes-associated protein (YAP); triglyceride; lipid; CtBP2; Hippo signaling; TEAD4; VGLL4; KRUPPEL-LIKE FACTOR; ADIPOCYTE DIFFERENTIATION; SIGNALING PATHWAY; FUNCTIONAL-ANALYSIS; HIPPO PATHWAY; SIZE-CONTROL; CELL FATE; GROWTH; RECEPTOR; EXPRESSION;

D O I：

10.1074/jbc.RA118.003608

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Hippo signaling pathway is known to play an important role in multiple physiological processes, including adipogenesis. However, whether the downstream components of the Hippo pathway are involved in adipogenesis remains unknown. Here we demonstrate that the TEA domain family (TEAD) transcription factors are essential for adipogenesis in murine 3T3-L1 preadipocytes. Knockdown of TEAD1-4 stimulated adipogenesis and increased the expression of adipocyte markers in these cells. Interestingly, we found that the TEAD4 knockdown-mediated adipogenesis proceeded in a Yes-associated protein (YAP)/TAZ (Wwtr1)-independent manner and that adipogenesis suppression in WT cells involved formation of a ternary complex comprising TEAD4 and the transcriptional cofactors C-terminal binding protein 2 (CtBP2) and vestigial-like family member 4 (VGLL4). VGLL4 acted as an adaptor protein that enhanced the interaction between TEAD4 and CtBP2, and this TEAD4-VGLL4-CtBP2 ternary complex dynamically existed at the early stage of adipogenesis. Finally, we verified that TEAD4 directly targets the promoters of major adipogenesis transcription factors such as peroxisome proliferator-activated receptor (PPAR) and adiponectin, C1Q, and collagen domain-containing (Adipoq) during adipogenesis. These findings reveal critical insights into the role of the TEAD4-VGLL4-CtBP2 transcriptional repressor complex in suppression of adipogenesis in murine preadipocytes.

引用

页码：17119 / 17134

页数：16

共 59 条

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