2. Academic Validation
  3. pVHL promotes lysosomal degradation of YAP in lung adenocarcinoma

pVHL promotes lysosomal degradation of YAP in lung adenocarcinoma

  • Cell Signal. 2021 Jul;83:110002. doi: 10.1016/j.cellsig.2021.110002.
Lan Hu 1,  Hao Wu 1,  Tian Jiang 2,  Mengzhen Kuang 1,  Bo Liu 1,  Xinying Guo 1,  Daochuan He 1,  Mengqian Chen 1,  Jie Gu 1,  Jianxin Gu 1,  Lei Chang 3,  Mingxiang Feng 4,  Yuanyuan Ruan 5
Affiliations

Affiliations

  • 1 NHC Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 2 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 3 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China. Electronic address: changlei@ncpsb.org.cn.
  • 4 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: feng.mingxiang@zs-hospital.sh.cn.
  • 5 NHC Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: yuanyuanruan@fudan.edu.cn.
PMID: 33823241 DOI: 10.1016/j.cellsig.2021.110002
Abstract

Yes-associated protein (YAP) is a vital transcriptional co-activator that activates cell proliferation and evasion of Apoptosis for the promotion of tumorigenesis. The von Hippel-Lindau tumor suppressor protein (pVHL), as a critical component of E3 ubiquitin Ligase, targets various substrates to regulate tumor progression. However, the precise molecular mechanisms of pVHL during tumorigenesis remain largely unclear. Herein, we found that there was a significant negative correlation between pVHL and YAP at protein level in the TCGA-LUAD dataset and our cohort. Over-expression of pVHL decreased YAP protein expression and reduced its transcriptional activity. Further study indicated that pVHL did not affect YAP mRNA level but decreased YAP protein stability in a lysosome-dependent manner. In addition, the pVHL-mediated degradation of YAP inhibited cellular proliferation, migration, and enhanced chemosensitivity to cisplatin in lung adenocarcinoma cells. Interestingly, the pVHL-mediated YAP degradation was blocked by elevated O-GlcNAcylation. Collectively, our findings demonstrate that pVHL modulates the lysosomal degradation of YAP, and may provide more clues to better understanding the tumor suppressive effects of pVHL.

Keywords

Lung adenocarcinoma; Lysosomal degradation; O-GlcNAcylation; YAP; pVHL.

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