A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis

Toshiro Moroishi, Hyun Woo Park, Baodong Qin, Qian Chen, Zhipeng Meng, Steven W. Plouffe, Koji Taniguchi, Fa Xing Yu, Michael Karin, Duojia Pan, Kun Liang Guan

研究成果: Article査読

191 被引用数 (Scopus)


YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. Aberrant hyperactivation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivation impairs tissue development and regeneration. Dynamic and precise control of YAP/TAZactivity is thus important to ensure proper physiological regulation and homeostasis of the cells. Here, we show that YAP/TAZ activation results in activation of their negative regulators, LATS1/2 (large tumor suppressor 1/2) kinases, to constitute a negative feedback loop of the Hippo pathway in both cultured cells and mouse tissues. YAP/TAZ in complex with the transcription factor TEAD (TEA domain family member) directly induce LATS2 expression. Furthermore, YAP/TAZ also stimulate the kinase activity of LATS1/2 through inducing NF2 (neurofibromin 2). This feedback regulation is responsible for the transient activation of YAP upon lysophosphatidic acid (LPA) stimulation and the inhibition of YAP-induced cell migration. Thus, this LATS-mediated feedback loop provides an efficient mechanism to establish the robustness and homeostasis of YAP/TAZ regulation.

ジャーナルGenes and Development
出版ステータスPublished - 2015 6 15

ASJC Scopus subject areas

  • 遺伝学
  • 発生生物学


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