替代性Wnt信号激活YAP/TAZ。
Alternative Wnt Signaling Activates YAP/TAZ.
作者信息
Park Hyun Woo, Kim Young Chul, Yu Bo, Moroishi Toshiro, Mo Jung-Soon, Plouffe Steven W, Meng Zhipeng, Lin Kimberly C, Yu Fa-Xing, Alexander Caroline M, Wang Cun-Yu, Guan Kun-Liang
机构信息
Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Department of Cardiology, Veterans Medical Research Foundation, San Diego, CA 92161, USA.
出版信息
Cell. 2015 Aug 13;162(4):780-94. doi: 10.1016/j.cell.2015.07.013.
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/β-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis" that consists of Wnt-FZD/ROR-Gα12/13-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/β-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling.
转录共激活因子YAP和TAZ是器官大小和组织稳态的关键调节因子，它们的失调会导致人类癌症。在此，我们发现YAP/TAZ是选择性Wnt信号通路真正的下游效应器。Wnt5a/b和Wnt3a可独立于经典Wnt/β-连环蛋白信号传导诱导YAP/TAZ激活。从机制上讲，我们描绘了“选择性Wnt-YAP/TAZ信号轴”，其由Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2组成，以促进YAP/TAZ激活和TEAD介导的转录。YAP/TAZ介导选择性Wnt信号的生物学功能，包括基因表达、成骨分化、细胞迁移以及对Wnt/β-连环蛋白信号的拮抗作用。总之，我们的研究确立了YAP/TAZ作为选择性Wnt信号的关键介质。
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