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Study of Protein-protein Interactions in Autophagy Research
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VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes

Tianyu Zhao1,2, Yuanyuan Guan1,2, Chenchen Xu1,2

  • 1State Key Laboratory of Membrane Biology, New Cornerstone Science Laboratory, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China.

Nature Communications
|December 20, 2023
PubMed

Insights

Scientists discovered VWCE, a novel regulator of cell growth signaling. Reduced VWCE levels are linked to prostate cancer, suggesting it as a potential therapeutic target for cancer treatment.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Cancer Research

Background:

  • The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and metabolism, sensing nutrient availability.
  • Dysregulation of mTORC1 signaling is implicated in metabolic diseases, cancer, and aging.
  • Amino acid signals activate mTORC1 via GATOR1 and GATOR2 complexes.

Purpose of the Study:

  • To identify novel regulators of amino acid-dependent mTORC1 signaling.
  • To investigate the role of VWCE in mTORC1 pathway and its association with prostate cancer.

Main Methods:

  • Investigated the function of VWCE in mTORC1 signaling.
  • Utilized knockdown experiments to assess VWCE's effect on mTORC1 activity.
  • Examined VWCE's interaction with the KICSTOR complex and GATOR1 recruitment.
  • Performed bioinformatic analysis on VWCE expression in prostate cancer.

Main Results:

  • Identified VWCE (von Willebrand factor C and EGF domains) as a negative regulator of mTORC1 signaling.
  • VWCE knockdown enhanced mTORC1 activity independently of amino acid availability.
  • VWCE facilitates GATOR1 recruitment to lysosomes via interaction with the KICSTOR complex.
  • Reduced VWCE expression was observed in prostate cancer tissues.

Conclusions:

  • VWCE acts as a crucial negative regulator in amino acid-mediated mTORC1 signaling.
  • VWCE's reduced expression in prostate cancer suggests a role in tumorigenesis.
  • Overexpression of VWCE inhibits prostate cancer development, positioning it as a potential therapeutic target.

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