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VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes

Author

Listed:
  • Tianyu Zhao

    (Peking University
    Peking University)

  • Yuanyuan Guan

    (Peking University
    Peking University)

  • Chenchen Xu

    (Peking University
    Peking University)

  • Dong Wang

    (Peking University
    Peking University)

  • Jialiang Guan

    (Peking University)

  • Ying Liu

    (Peking University
    Peking University
    Beijing Advanced Innovation Center for Genomics)

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 through sensor proteins and two protein complexes named GATOR1 and GATOR2. In this study, we identify VWCE (von Willebrand factor C and EGF domains) as a negative regulator of amino acid-dependent mTORC1 signaling. Knockdown of VWCE promotes mTORC1 activity even in the absence of amino acids. VWCE interacts with the KICSTOR complex to facilitate the recruitment of GATOR1 to the lysosomes. Bioinformatic analysis reveals that expression of VWCE is reduced in prostate cancer. More importantly, overexpression of VWCE inhibits the development of prostate cancer. Therefore, VWCE may serve as a potential therapeutic target for the treatment of prostate cancers.

Suggested Citation

  • Tianyu Zhao & Yuanyuan Guan & Chenchen Xu & Dong Wang & Jialiang Guan & Ying Liu, 2023. "VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44241-8
    DOI: 10.1038/s41467-023-44241-8
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    References listed on IDEAS

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    1. Rachel L. Wolfson & Lynne Chantranupong & Gregory A. Wyant & Xin Gu & Jose M. Orozco & Kuang Shen & Kendall J. Condon & Sabrina Petri & Jibril Kedir & Sonia M. Scaria & Monther Abu-Remaileh & Wayne N., 2017. "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1," Nature, Nature, vol. 543(7645), pages 438-442, March.
    2. Min Peng & Na Yin & Ming O. Li, 2017. "SZT2 dictates GATOR control of mTORC1 signalling," Nature, Nature, vol. 543(7645), pages 433-437, March.
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