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Review
. 2020 Oct 22;21(21):7842.
doi: 10.3390/ijms21217842.

Role of Post-Translational Modifications of cGAS in Innate Immunity

Yakun Wu  1 , Shitao Li  1
Affiliations
Review

Role of Post-Translational Modifications of cGAS in Innate Immunity

Yakun Wu et al. Int J Mol Sci. .

Abstract

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.

Keywords: acetylation; cGAS; glutamylation; innate immunity; phosphorylation; post-translational modification; sumoylation; ubiquitination.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The cytosolic DNA sensing pathway mediated by cyclic GMP–AMP synthase (cGAS).
Figure 2
Figure 2
PTMs play a critical role in regulating cGAS enzymatic activity, DNA binding, protein stability and subcellular localization.
See this image and copyright information in PMC

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