The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.
The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.
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DOI：
10.1084/jem.20180139
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发表时间：
2018-05-07
期刊：
影响因子：
--
通讯作者：
Chen ZJ
中科院分区：
文献类型：
--
作者：
Li T;Chen ZJ
cGAS - cGAMP - STING通路介导对胞质DNA的免疫和炎症反应。本综述总结了关于基因组不稳定性如何导致cGAS激活以及该通路如何关键地将DNA损伤与自身炎症性疾病、细胞衰老和癌症联系起来的最新研究结果。
微生物DNA的检测是一种进化上保守的机制，它提醒宿主免疫系统对微生物感染发起防御反应。然而，这种检测机制也给宿主带来了一个挑战，即如何区分外来DNA和大量的自身DNA。环鸟苷酸（GMP） - 腺苷酸（AMP）合酶（cGAS）是一种DNA传感器，它通过产生第二信使环GMP - AMP（cGAMP）来触发先天免疫反应，cGAMP结合并激活衔接蛋白STING。然而，无论序列如何，双链DNA都能激活cGAS，包括自身DNA。尽管细胞中cGAS通常如何保持无活性仍未被充分理解，但近期研究提供了强有力的证据表明基因组DNA损伤会导致cGAS激活以刺激炎症反应。本综述总结了关于基因组不稳定性和DNA损伤如何触发cGAS激活以及cGAS如何作为从DNA损伤到炎症、细胞衰老和癌症的联系的最新研究结果。
The cGAS–cGAMP–STING pathway mediates immune and inflammatory responses to cytosolic DNA. This review summarizes recent findings on how genomic instability leads to cGAS activation and how this pathway critically connects DNA damage to autoinflammatory diseases, cellular senescence, and cancer. Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response to microbial infections. However, this detection mechanism also poses a challenge to the host as to how to distinguish foreign DNA from abundant self-DNA. Cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS) is a DNA sensor that triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the adaptor protein STING. However, cGAS can be activated by double-stranded DNA irrespective of the sequence, including self-DNA. Although how cGAS is normally kept inactive in cells is still not well understood, recent research has provided strong evidence that genomic DNA damage leads to cGAS activation to stimulate inflammatory responses. This review summarizes recent findings on how genomic instability and DNA damage trigger cGAS activation and how cGAS serves as a link from DNA damage to inflammation, cellular senescence, and cancer.
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影响因子：
11.2
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
通讯作者：
Auh SL
影响因子：
8.8
作者：
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通讯作者：
van Deursen JM
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T