Regulation of cGAS Activity and Downstream Signaling.

Regulation of cGAS Activity and Downstream Signaling.
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cGAS活性和下游信号传导的调节。

DOI:
10.3390/cells11182812
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发表时间:
2022-09-08
期刊:
影响因子:
6
通讯作者:
Mehta, Dolly
Mehta, Dolly
中科院分区:
生物学2区
文献类型:
--
作者:
Joshi, Bhagwati;Joshi, Jagdish Chandra;Mehta, Dolly

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环GMP-AMP合成酶(cGAS)是一种主要的、普遍表达的细胞质dna传感器,通过产生第二信使环GMP-AMP (cGAMP)和干扰素基因刺激因子(STING)来激活先天免疫反应。cGAS含有一个高度无序的n端,可以感知基因组/染色质DNA,而cGAS的C端结合从各种来源释放的dsDNA,包括线粒体、病原体和死细胞。此外,cGAS的细胞定位决定了它对外源dna和自身dna的反应。最近的证据也强调了ddna诱导的cGAS翻译后修饰在调节炎症反应中的重要性。本文从结构、亚细胞定位、翻译后机制和Ca2+信号传导等方面对cGAS活性调控进行了综述和分析。我们还讨论了cGAS激活在不同疾病和临床结果中的作用。
Cyclic GMP-AMP synthase (cGAS) is a predominant and ubiquitously expressed cytosolic onfirmedDNA sensor that activates innate immune responses by producing a second messenger, cyclic GMP-AMP (cGAMP), and the stimulator of interferon genes (STING). cGAS contains a highly disordered N-terminus, which can sense genomic/chromatin DNA, while the C terminal of cGAS binds dsDNA liberated from various sources, including mitochondria, pathogens, and dead cells. Furthermore, cGAS cellular localization dictates its response to foreign versus self-DNA. Recent evidence has also highlighted the importance of dsDNA-induced post-translational modifications of cGAS in modulating inflammatory responses. This review summarizes and analyzes cGAS activity regulation based on structure, sub-cellular localization, post-translational mechanisms, and Ca2+ signaling. We also discussed the role of cGAS activation in different diseases and clinical outcomes.
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