ID | 116604 |
Author |
Han, Zhu
Sichuan University
Zhang, Weizhi
Huazhong University of Science and Technology
Ning, Wanshan
Huazhong University of Science and Technology
Wang, Chenwei
Huazhong University of Science and Technology
Deng, Wankun
Huazhong University of Science and Technology
Li, Zhidan
Sichuan University
Shang, Zehua
Sichuan University
Shen, Xiaofei
Chengdu University
Liu, Xiaohui
Tsinghua University
Baba, Otto
Tokushima University
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Morita, Tsuyoshi
Tokushima University
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Chen, Lu
Sichuan University
Xue, Yu
Huazhong University of Science and Technology|Nanjing University
Jia, Da
Sichuan University
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Content Type |
Journal Article
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Description | Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.
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Journal Title |
Nature Communications
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ISSN | 20411723
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NCID | AA12645905
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Publisher | Springer Nature
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Volume | 12
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Start Page | 3258
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Published Date | 2021-05-31
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Rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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language |
eng
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departments |
Oral Sciences
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