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The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction.
Wu, Mengying; Hu, Liqiao; He, Lingli; Yuan, Liang; Yang, Lingling; Zhao, Bin; Zhang, Lei; He, Xiaojing.
Affiliation
  • Wu M; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • Hu L; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. Electronic address: liq@hust.edu.cn.
  • He L; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Yuan L; College of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yang L; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • Zhao B; The MOE Key Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
  • Zhang L; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; College of Life Science and Technology, ShanghaiTech University, Shangh
  • He X; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. Electronic address: hexj@hust.edu.cn.
J Biol Chem ; 300(5): 107212, 2024 May.
Article in En | MEDLINE | ID: mdl-38522513
ABSTRACT
As an output effector of the Hippo signaling pathway, the TEAD transcription factor and co-activator YAP play crucial functions in promoting cell proliferation and organ size. The tumor suppressor NF2 has been shown to activate LATS1/2 kinases and interplay with the Hippo pathway to suppress the YAP-TEAD complex. However, whether and how NF2 could directly regulate TEAD remains unknown. We identified a direct link and physical interaction between NF2 and TEAD4. NF2 interacted with TEAD4 through its FERM domain and C-terminal tail and decreased the protein stability of TEAD4 independently of LATS1/2 and YAP. Furthermore, NF2 inhibited TEAD4 palmitoylation and induced the cytoplasmic translocation of TEAD4, resulting in ubiquitination and dysfunction of TEAD4. Moreover, the interaction with TEAD4 is required for NF2 function to suppress cell proliferation. These findings reveal an unanticipated role of NF2 as a binding partner and inhibitor of the transcription factor TEAD, shedding light on an alternative mechanism of how NF2 functions as a tumor suppressor through the Hippo signaling cascade.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Protein Serine-Threonine Kinases / Neurofibromin 2 / Hippo Signaling Pathway / TEA Domain Transcription Factors Limits: Humans Language: En Journal: J Biol Chem Year: 2024 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Protein Serine-Threonine Kinases / Neurofibromin 2 / Hippo Signaling Pathway / TEA Domain Transcription Factors Limits: Humans Language: En Journal: J Biol Chem Year: 2024 Type: Article Affiliation country: China