| Item type |
文献 / Documents(1) |
| 公開日 |
2022-01-28 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1038/s41467-021-23539-5 |
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関連名称 |
10.1038/s41467-021-23539-5 |
| 出版タイプ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Model-based analysis uncovers mutations altering autophagy selectivity in human cancer |
| 著者 |
Han, Zhu
Zhang, Weizhi
Ning, Wanshan
Wang, Chenwei
Deng, Wankun
Li, Zhidan
Shang, Zehua
Shen, Xiaofei
Liu, Xiaohui
馬場, 麻人
守田, 剛
Chen, Lu
Xue, Yu
Jia, Da
|
| 抄録 |
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内容記述 |
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. |
| 書誌情報 |
en : Nature Communications
巻 12,
p. 3258,
発行日 2021-05-31
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
20411723 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA12645905 |
| 出版者 |
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出版者 |
Springer Nature |
| 権利情報 |
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|
権利情報 |
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/. |
| EID |
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識別子 |
375988 |
| 言語 |
|
|
言語 |
eng |
ncomms_12_3258.pdf (4.28 MB)
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