先天免疫系统
细胞生物学
干扰素基因刺激剂
DNA
免疫系统
生物
干扰素
鸟苷
基因敲除
信号转导
生物化学
免疫学
基因
作者
Jie Zhang,Er-Chi Zhou,Yan He,Ze-Lin Chai,Ben-Zhe Ji,Tao Yi,Han-Ling Wang,Wen-Qiang Wu,Yong Liu,Xinghua Zhang,Yu Liu
出处
期刊:Cell Reports
[Elsevier]
日期:2023-03-01
卷期号:42 (3): 112278-112278
被引量:3
标识
DOI:10.1016/j.celrep.2023.112278
摘要
As a key dsDNA recognition receptor, cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) plays a vital role in innate immune responses. Activated cGAS, by sensing DNA, catalyzes the synthesis of the secondary messenger cyclic GMP-AMP (cGAMP), which subsequently activates downstream signaling to induce production of interferons and inflammatory cytokines. Here, we report Zyg-11 family member B (ZYG11B) as a potent amplifier in cGAS-mediated immune responses. Knockdown of ZYG11B impairs production of cGAMP and subsequent transcription of interferon and inflammatory cytokines. Mechanistically, ZYG11B enhances cGAS-DNA binding affinity, potentiates cGAS-DNA condensation, and stabilizes the cGAS-DNA condensed complex. Moreover, herpes simplex virus 1 (HSV-1) infection induces ZYG11B degradation in a cGAS-unrelated manner. Our findings not only reveal an important role of ZYG11B in the early stage of DNA-induced cGAS activation but also indicate a viral strategy to dampen the innate immune response.
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