Regulation of cGAS Activity and Downstream Signaling

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...

Full description

Saved in:
Bibliographic Details
Published inCells (Basel, Switzerland) Vol. 11; no. 18; p. 2812
Main Authors Joshi, Bhagwati, Joshi, Jagdish Chandra, Mehta, Dolly
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.09.2022
MDPI
Subjects
Amino acids
autoimmunity
calcium
Calcium signalling
Cellular signal transduction
cGAS
Chromatin
Cyclic GMP
Enzymes
Genetic aspects
Genetic regulation
Health aspects
Immune response
Inflammation
Innate immunity
Interferon
Localization
Mitochondria
Mitochondrial DNA
N-Terminus
Plasma
Post-translation
Review
RNA polymerase
Sensors
STING
Translation
Viral infections
United States
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-2
These authors contributed equally to this work.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11182812