From Wikipedia, the free encyclopedia
Cytosolic DNA sensor
Cyclic GMP-AMP synthase (cGAS,
cGAMP synthase), belonging to the
nucleotidyltransferase family, is a
cytosolic DNA sensor that activates a
type-I interferon response. It is part of the
cGAS-STING DNA sensing pathway. It binds to microbial
DNA as well as self DNA that invades the
cytoplasm, and catalyzes
cGAMP synthesis.
[1]
cGAMP then functions as a
second messenger that binds to and activates the
endoplasmic reticulum protein
STING to trigger
type-I IFNs production.
[2]
[3]
[4] Mice lacking cGAS are more vulnerable to lethal infection by
DNA viruses and
RNA viruses.
[5]
[6] In addition, cGAS has been shown to be an innate immune sensor of retroviruses including
HIV.
[7]
[8] The human gene encoding cGAS is
MB21D1 on chromosome 6.
References
-
^ Sun L, Wu J, Du F, Chen X, Chen ZJ (February 2013).
"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 339 (6121): 786–91.
Bibcode:
2013Sci...339..786S.
doi:
10.1126/science.1232458.
PMC
3863629.
PMID
23258413.
-
^ Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ (February 2013).
"Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA". Science. 339 (6121): 826–30.
Bibcode:
2013Sci...339..826W.
doi:
10.1126/science.1229963.
PMC
3855410.
PMID
23258412.
-
^ Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, et al. (May 2013).
"Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase". Cell. 153 (5): 1094–107.
doi:
10.1016/j.cell.2013.04.046.
PMC
4382009.
PMID
23647843.
-
^ Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, Chen ZJ (July 2013).
"Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING". Molecular Cell. 51 (2): 226–35.
doi:
10.1016/j.molcel.2013.05.022.
PMC
3808999.
PMID
23747010.
-
^ Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ (September 2013).
"Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects". Science. 341 (6152): 1390–4.
Bibcode:
2013Sci...341.1390L.
doi:
10.1126/science.1244040.
PMC
3863637.
PMID
23989956.
-
^ Yu P, Miao Z, Li Y, Bansal R, Peppelenbosch MP, Pan Q (January 2021).
"cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages". Gut Microbes. 13 (1): 1959839.
doi:
10.1080/19490976.2021.1959839.
PMC
8344765.
PMID
34347572.
-
^ Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, et al. (August 2013).
"Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses". Science. 341 (6148): 903–6.
Bibcode:
2013Sci...341..903G.
doi:
10.1126/science.1240933.
PMC
3860819.
PMID
23929945.
-
^ Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, et al. (December 2013).
"The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells". Immunity. 39 (6): 1132–42.
doi:
10.1016/j.immuni.2013.11.002.
PMID
24269171.