Role of Post-Translational Modifications of cGAS in Innate Immunity.

Role of Post-Translational Modifications of cGAS in Innate Immunity.
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DOI:
10.3390/ijms21217842
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发表时间:
2020-10-22
影响因子:
5.6
通讯作者:
Li S
Li S
中科院分区:
生物学2区
文献类型:
--
作者:
Wu Y;Li S

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环GMP-AMP合酶(cGAS)是在DNA结合时产生第二信使环GMP-AMP(cGAMP)的合酶。cGAS最初被发现是作为细胞溶质DNA传感器,其检测暴露在细胞质中的来自病原体或细胞损伤的DNA。活化的cGAS引发信号传导级联以活化I型干扰素(IFN)表达,这对于宿主防御和自身免疫性疾病至关重要。此外,cGAS在衰老、DNA修复、细胞凋亡和肿瘤发生中起作用。最近,已经报道了cGAS的各种翻译后修饰(PTM),例如磷酸化、泛素化、乙酰化、谷氨酰化和类小泛素化。这些PTM深刻地影响cGAS功能。因此,在这里,我们回顾了最近报道的cGAS的PTM以及这些PTM如何调节cGAS酶活性,DNA结合和蛋白质稳定性,并讨论了潜在的未来方向。
Cyclic GMP–AMP synthase (cGAS) is the synthase that generates the second messenger cyclic GMP–AMP (cGAMP) upon DNA binding. cGAS was first discovered as the cytosolic DNA sensor that detects DNA exposed in the cytoplasm either from pathogens or cellular damage. Activated cGAS instigates the signaling cascades to activate type I interferon (IFN) expression, critical for host defense and autoimmune diseases. In addition, cGAS plays a role in senescence, DNA repair, apoptosis, and tumorigenesis. Recently, various post-translational modifications (PTMs) of cGAS have been reported, such as phosphorylation, ubiquitination, acetylation, glutamylation, and sumoylation. These PTMs profoundly affect cGAS functions. Thus, here we review the recent reported PTMs of cGAS and how these PTMs regulate cGAS enzymatic activity, DNA binding, and protein stability, and discuss the potential future directions.
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