| Title | VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes |
| Authors | Zhao, Tianyu Guan, Yuanyuan Xu, Chenchen Wang, Dong Guan, Jialiang Liu, Ying |
| Affiliation | Peking Univ, Inst Mol Med, Coll Future Technol, State Key Lab Membrane Biol,New Cornerstone Sci La, Beijing 100871, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, PKU Tsinghua NIBS Grad Program, Beijing 100871, Peoples R China Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China |
| Keywords | RAG GTPASES COMPLEX GROWTH |
| Issue Date | 20-Dec-2023 |
| Publisher | NATURE COMMUNICATIONS |
| 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. mTORC1 adapts cellular metabolism in response to nutrient signals. Here, the authors identify VWCE as a negative regulator of amino acid-dependent mTORC1 signaling and a potential as a therapeutic target in prostate cancer treatments. |
| URI | http://hdl.handle.net/20.500.11897/693644 |
| DOI | 10.1038/s41467-023-44241-8 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 膜生物学国家重点实验室 前沿交叉学科研究院 |
