NAT IMMUNOL:山东大学赵伟团队发现,GPX4诱导STING的激活。

2020-06-22 MedSci原创 MedSci原创

来自山东大学的赵伟团队发现,由谷胱甘肽过氧化物酶4(GPX4)维持的细胞氧化还原平衡是STING激活所必需的。

干扰素基因刺激器(STING)对于感知细胞核DNA和启动先天性免疫反应,以对抗微生物感染和肿瘤至关重要。氧化还原平衡是所有生命系统中存在的氧化反应和还原反应的平衡。然而,至今为止,关于细胞内氧化还原状态如何控制STING激活尚不清楚。

最近,来自山东大学的赵伟团队发现,由谷胱甘肽过氧化物酶4(GPX4)维持的细胞氧化还原平衡是STING激活所必需的。GPX4的缺乏增强了细胞脂质过氧化,从而特异性地抑制了cGAS-STING途径。

与此一致,GPX4的缺乏抑制了单纯疱疹病毒-1(HSV-1)诱导的先天性抗病毒免疫反应,并促进HSV-1在体内的复制。

从机制上讲,GPX4失活增加了脂质过氧化的产生,导致STING在C88处羰基化,并抑制其从内质网(ER)向高尔基复合体的运输。

因此,细胞应激诱导的脂质过氧化会特异性地减弱STING的DNA感应途径,这表明GPX4通过维持脂质的氧化还原平衡来促进STING的激活。

 

原始出处:

Mutian Jia et al. Redox homeostasis maintained by GPX4 facilitates STING activation, Nature Immunology (2020).

 

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    2021-06-02 imp_xiaoww

    是不是也会和放疗抵抗有关

    0

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    2020-10-01 liye789132251
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    2020-06-24 huangshifeng
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    2020-06-24 lxg955

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