Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL, PNAS, 115(12):E2762-E2771,5 Mar 2018
发布时间：2018年03月07日
PNAS, 115(12):E2762-E2771,5 Mar 2018，DOI: 10.1073/pnas.1716439115
Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL
Yanfang Wu, Xia Li, Junying Jia, Yanpeng Zhang, Jing Li, Zhengmao Zhu, Huaqing Wang, Jie Tang and Junjie Hu
Abstract
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a pathological condition observed in many diseases, including cancer, diabetes, and neurodegenerative diseases. Failure to relieve the cellular stress via adaptive mechanisms of the unfolded protein response (UPR) activates apoptotic cell death. We demonstrate that a membrane-anchored RING finger protein, RNF183, is specifically induced by prolonged ER stress. RNF183 is regulated by IRE1, mainly through miR-7. As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis. Our findings imply that manipulation of RNF183 activity may help control cell fate in pathological conditions and suggest that the close contact between the ER and mitochondria plays a key role in cellular signaling.
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Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL, PNAS, 115(12):E2762-E2771,5 Mar 2018
PNAS, 115(12):E2762-E2771,5 Mar 2018，DOI: 10.1073/pnas.1716439115
Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL
Yanfang Wu, Xia Li, Junying Jia, Yanpeng Zhang, Jing Li, Zhengmao Zhu, Huaqing Wang, Jie Tang and Junjie Hu
Abstract
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a pathological condition observed in many diseases, including cancer, diabetes, and neurodegenerative diseases. Failure to relieve the cellular stress via adaptive mechanisms of the unfolded protein response (UPR) activates apoptotic cell death. We demonstrate that a membrane-anchored RING finger protein, RNF183, is specifically induced by prolonged ER stress. RNF183 is regulated by IRE1, mainly through miR-7. As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis. Our findings imply that manipulation of RNF183 activity may help control cell fate in pathological conditions and suggest that the close contact between the ER and mitochondria plays a key role in cellular signaling.
文章链接：http://www.pnas.org/content/early/2018/03/01/1716439115
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