ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization

被引:682
作者
Sun, Wenxiang [1 ]
Li, Yang [1 ]
Chen, Lu [1 ]
Chen, Huihui [1 ]
You, Fuping [1 ]
Zhou, Xiang [1 ]
Zhou, Yi [1 ]
Zhai, Zhonghe [1 ]
Chen, Danying [1 ]
Jiang, Zhengfan [1 ]
机构
[1] Peking Univ, Sch Life Sci, Educ Minist, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
innate immunity; type I IFN; functional cDNA library screening; cytosolic RNA and dsDNA; ER retention signal; NF-KAPPA-B; DOUBLE-STRANDED-RNA; RIG-I; ADAPTER PROTEIN; ANTIVIRAL RESPONSE; MEMBRANE-PROTEINS; VIRUS; RECOGNITION; RECEPTORS; DNA;
D O I
10.1073/pnas.0900850106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We report here the identification and characterization of a protein, ERIS, an endoplasmic reticulum (ER) IFN stimulator, which is a strong type I IFN stimulator and plays a pivotal role in response to both non-self-cytosolic RNA and dsDNA. ERIS (also known as STING or MITA) resided exclusively on ER membrane. The ER retention/retrieval sequence RIR was found to be critical to retain the protein on ER membrane and to maintain its integrity. ERIS was dimerized on innate immune challenges. Coumermycin-induced ERIS dimerization led to strong and fast IFN induction, suggesting that dimerization of ERIS was critical for self-activation and subsequent downstream signaling.
引用
收藏
页码:8653 / 8658
页数:6
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