Alternative Wnt Signaling Activates YAP/TAZ

被引：699

作者：

Park, Hyun Woo ^{[1
,2
]}

Kim, Young Chul ^{[1
,2
,3
]}

Yu, Bo ^{[4
]}

Moroishi, Toshiro ^{[1
,2
]}

Mo, Jung-Soon ^{[1
,2
]}

Plouffe, Steven W. ^{[1
,2
]}

Meng, Zhipeng ^{[1
,2
]}

Lin, Kimberly C. ^{[1
,2
]}

Yu, Fa-Xing ^{[5
,6
]}

Alexander, Caroline M. ^{[7
]}

Wang, Cun-Yu ^{[4
]}

Guan, Kun-Liang ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[3] Vet Med Res Fdn, Dept Cardiol, San Diego, CA 92161 USA

[4] Univ Calif Los Angeles, Div Oral Biol & Med, Lab Mol Signaling, Los Angeles, CA 90095 USA

[5] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China

[6] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

[7] Univ Wisconsin Madison, Sch Med & Publ Hlth, McArdle Lab Canc Res, Madison, WI 53706 USA

来源：

CELL | 2015年 / 162卷 / 04期

关键词：

PROTEIN-INTERACTION NETWORK; HIPPO-YAP PATHWAY; STEM-CELLS; GASTRULATION; INHIBITION; TAZ; ADIPOGENESIS; REGENERATION; MECHANISMS; FRIZZLED-1;

D O I：

10.1016/j.cell.2015.07.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer. Here, we discover YAP/TAZ as bona fide downstream effectors of the alternative Wnt signaling pathway. Wnt5a/b and Wnt3a induce YAP/TAZ activation independent of canonical Wnt/beta-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis'' that consists of Wnt-FZD/ROR-Ga alpha(12/13)-Rho GTPases-Lats1/2 to promote YAP/TAZ activation and TEAD-mediated transcription. YAP/TAZ mediate the biological functions of alternative Wnt signaling, including gene expression, osteogenic differentiation, cell migration, and antagonism of Wnt/beta-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling.

引用

页码：780 / 794

页数：15

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