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

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1271-1284
Number of pages14
JournalGenes and Development
Volume29
Issue number12
DOIs
Publication statusPublished - 2015 Jun 15

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Homeostasis
Proteins
Phosphotransferases
Long-Acting Thyroid Stimulator
Neurofibromin 2
Neoplasms
Organ Size
Cell Movement
Regeneration
Cultured Cells
Carcinogenesis
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

Moroishi, T., Park, H. W., Qin, B., Chen, Q., Meng, Z., Plouffe, S. W., ... Guan, K. L. (2015). A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes and Development, 29(12), 1271-1284. https://doi.org/10.1101/gad.262816.115
Moroishi, Toshiro ; Park, Hyun Woo ; Qin, Baodong ; Chen, Qian ; Meng, Zhipeng ; Plouffe, Steven W. ; Taniguchi, Koji ; Yu, Fa Xing ; Karin, Michael ; Pan, Duojia ; Guan, Kun Liang. / A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. In: Genes and Development. 2015 ; Vol. 29, No. 12. pp. 1271-1284.
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Moroishi, T, Park, HW, Qin, B, Chen, Q, Meng, Z, Plouffe, SW, Taniguchi, K, Yu, FX, Karin, M, Pan, D & Guan, KL 2015, 'A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis', Genes and Development, vol. 29, no. 12, pp. 1271-1284. https://doi.org/10.1101/gad.262816.115

A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. / Moroishi, Toshiro; Park, Hyun Woo; Qin, Baodong; Chen, Qian; Meng, Zhipeng; Plouffe, Steven W.; Taniguchi, Koji; Yu, Fa Xing; Karin, Michael; Pan, Duojia; Guan, Kun Liang.

In: Genes and Development, Vol. 29, No. 12, 15.06.2015, p. 1271-1284.

Research output: Contribution to journalArticle

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AU - Moroishi, Toshiro

AU - Park, Hyun Woo

AU - Qin, Baodong

AU - Chen, Qian

AU - Meng, Zhipeng

AU - Plouffe, Steven W.

AU - Taniguchi, Koji

AU - Yu, Fa Xing

AU - Karin, Michael

AU - Pan, Duojia

AU - Guan, Kun Liang

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Y1 - 2015/6/15

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