Molecules and Cells

  • 제46권10호
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  • Pages.592-610
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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The TGFβ→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1

  • Min-Kyu Kim (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Sang-Hyun Han (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Tae-Geun Park (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Soo-Hyun Song (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Ja-Youl Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • You-Soub Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Seo-Yeong Yoo (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Xin-Zi Chi (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Eung-Gook Kim (Department of Biochemistry, College of Medicine and Medical Research Center, Chungbuk National University) ;
  • Ju-Won Jang (Department of Biomedical Science, Cheongju University) ;
  • Dae Sik Lim (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Andre J. van Wijnen (Department of Biochemistry, University of Vermont) ;
  • Jung-Won Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Suk-Chul Bae (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University)
  • 투고 : 2023.05.25
  • 심사 : 2023.07.25
  • 발행 : 2023.10.31
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초록

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

키워드

과제정보

S.-C.B. is supported by a Creative Research Grant (NRF-2014R1A3A2030690) through the National Research Foundation (NRF) of Korea. J.-W.L. is supported by Basic Science Research Program grant (NRF-2021R1I1A1A01060610) of Korea. M.-K.K. is supported by Basic Science Research Program grant (NRF-2017R1A6A3A11028050) of Korea. S.-H.S. is supported by Basic Science Research Program grant (NRF-2021R1I1A1A01059185). E.-G.K. is supported by Medical Research Center (MRC-2020R1A5A2017476) of Korea. D.-S. L. is supported by the National Creative Research Initiatives (NRF-2020-2079551) of Korea.

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