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[[File:CGAS complexed with dsDNA.png|thumbnail|cGAS complexed with dsDNA (Based on PDB 4O6A)]]
[[File:CGAS complexed with dsDNA.png|thumbnail|cGAS complexed with dsDNA (Based on PDB 4O6A)]]
[[File:cGAS-cGAMP-STING pathway.jpg|thumb|cGAS-cGAMP-STING pathway]]
[[File:cGAS-cGAMP-STING pathway.jpg|thumb|cGAS-cGAMP-STING pathway]]
'''Cyclic GMP-AMP synthase''' (cGAS, [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthase), belonging to the [[nucleotidyltransferase]] family, is a [[The cGAS – STING cytosolic DNA sensing pathway|cytosolic DNA sensor]] that activates the [[Interferon type I|type-I interferon]] pathway. It binds to microbial [[DNA]] as well as self DNA that invades the [[cytoplasm]], and catalyzes [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthesis.<ref name="pmid23258413">{{cite journal|last=Sun|first=L|author2=Wu, J |author3=Du, F |author4=Chen, X |author5= Chen, ZJ |title=Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=786–91|pmid=23258413|doi=10.1126/science.1232458}}</ref> [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] then functions as a [[second messenger]] that binds to and activates the [[endoplasmic reticulum]] protein STING to trigger type-I IFNs production.<ref name="pmid23258412">{{cite journal|last=Wu|first=J|author2=Sun, L |author3=Chen, X |author4=Du, F |author5=Shi, H |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=826–30|pmid=23258412|doi=10.1126/science.1229963}}</ref><ref name="GaoAscano2013">{{cite journal|last1=Gao|first1=Pu|last2=Ascano|first2=Manuel|last3=Wu|first3=Yang|last4=Barchet|first4=Winfried|last5=Gaffney|first5=Barbara L.|last6=Zillinger|first6=Thomas|last7=Serganov|first7=Artem A.|last8=Liu|first8=Yizhou|last9=Jones|first9=Roger A.|last10=Hartmann|first10=Gunther|last11=Tuschl|first11=Thomas|last12=Patel|first12=Dinshaw J.|title=Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase|journal=Cell|volume=153|issue=5|year=2013|pages=1094–1107|issn=00928674|doi=10.1016/j.cell.2013.04.046}}</ref>
'''Cyclic GMP-AMP synthase''' (cGAS, [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthase), belonging to the [[nucleotidyltransferase]] family, is a [[The cGAS – STING cytosolic DNA sensing pathway|cytosolic DNA sensor]] that activates the [[Interferon type I|type-I interferon]] pathway. It binds to microbial [[DNA]] as well as self DNA that invades the [[cytoplasm]], and catalyzes [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthesis.<ref name="pmid23258413">{{cite journal|last=Sun|first=L|author2=Wu, J |author3=Du, F |author4=Chen, X |author5= Chen, ZJ |title=Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=786–91|pmid=23258413|doi=10.1126/science.1232458}}</ref> [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] then functions as a [[second messenger]] that binds to and activates the [[endoplasmic reticulum]] protein STING to trigger type-I IFNs production.<ref name="pmid23258412">{{cite journal|last=Wu|first=J|author2=Sun, L |author3=Chen, X |author4=Du, F |author5=Shi, H |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=826–30|pmid=23258412|doi=10.1126/science.1229963}}</ref><ref name="GaoAscano2013">{{cite journal|last1=Gao|first1=Pu|last2=Ascano|first2=Manuel|last3=Wu|first3=Yang|last4=Barchet|first4=Winfried|last5=Gaffney|first5=Barbara L.|last6=Zillinger|first6=Thomas|last7=Serganov|first7=Artem A.|last8=Liu|first8=Yizhou|last9=Jones|first9=Roger A.|last10=Hartmann|first10=Gunther|last11=Tuschl|first11=Thomas|last12=Patel|first12=Dinshaw J.|title=Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase|journal=Cell|volume=153|issue=5|year=2013|pages=1094–1107|issn=0092-8674|doi=10.1016/j.cell.2013.04.046}}</ref>
<ref name=Zhang>{{cite journal|last=Zhang|first=X|author2=Shi, H |author3=Wu, J |author4=Zhang, X |author5=Sun, L |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING|journal=Molecular Cell|date=Jun 3, 2013|volume=51|issue=2|pages=226–235|doi=10.1016/j.molcel.2013.05.022}}</ref> Mice lacking cGAS were more vulnerable to lethal infection by DNA viruses.<ref name=Li>{{cite journal|last=Li|first=XD|author2=Wu, J |author3=Gao, D |author4=Wang, H |author5=Sun, L |author6= Chen, ZJ |title=Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects|journal=Science|date=Sep 20, 2013|volume=341|issue=6152|pages=1390–4|doi=10.1126/science.1244040 |pmid=23989956 |pmc=3863637}}</ref> In addition, cGAS has been shown to be an innate immune sensor of retroviruses including [[HIV]].<ref name=Gao>{{cite journal|last=Gao|first=D|author2=Wu, J |author3=Wu, YT |author4=Du, F |author5=Aroh, C |author6=Yan, N |author7=Sun, L |author8= Chen, ZJ |title=Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses|journal=Science|date=Aug 23, 2013|volume=341|issue=6148|pages=903–6|doi=10.1126/science.1240933 |pmid=23929945 |pmc=3860819}}</ref><ref name=Lahaye>{{cite journal|last=Lahaye|first=X|author2=Satoh, T |author3=Gentili, M |author4=Cerboni, S |author5=Conrad, C |author6=Hurbain, I |author7=El Marjou, A |author8=Lacabaratz, C |author9=Lelièvre, JD |author10=Manel, N |title=The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells|journal=Immunity|date=Dec 12, 2013|volume=39|issue=6|pages=1132–42|doi=10.1016/j.immuni.2013.11.002}}</ref>
<ref name=Zhang>{{cite journal|last=Zhang|first=X|author2=Shi, H |author3=Wu, J |author4=Zhang, X |author5=Sun, L |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING|journal=Molecular Cell|date=Jun 3, 2013|volume=51|issue=2|pages=226–235|doi=10.1016/j.molcel.2013.05.022}}</ref> Mice lacking cGAS were more vulnerable to lethal infection by DNA viruses.<ref name=Li>{{cite journal|last=Li|first=XD|author2=Wu, J |author3=Gao, D |author4=Wang, H |author5=Sun, L |author6= Chen, ZJ |title=Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects|journal=Science|date=Sep 20, 2013|volume=341|issue=6152|pages=1390–4|doi=10.1126/science.1244040 |pmid=23989956 |pmc=3863637}}</ref> In addition, cGAS has been shown to be an innate immune sensor of retroviruses including [[HIV]].<ref name=Gao>{{cite journal|last=Gao|first=D|author2=Wu, J |author3=Wu, YT |author4=Du, F |author5=Aroh, C |author6=Yan, N |author7=Sun, L |author8= Chen, ZJ |title=Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses|journal=Science|date=Aug 23, 2013|volume=341|issue=6148|pages=903–6|doi=10.1126/science.1240933 |pmid=23929945 |pmc=3860819}}</ref><ref name=Lahaye>{{cite journal|last=Lahaye|first=X|author2=Satoh, T |author3=Gentili, M |author4=Cerboni, S |author5=Conrad, C |author6=Hurbain, I |author7=El Marjou, A |author8=Lacabaratz, C |author9=Lelièvre, JD |author10=Manel, N |title=The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells|journal=Immunity|date=Dec 12, 2013|volume=39|issue=6|pages=1132–42|doi=10.1016/j.immuni.2013.11.002}}</ref>


Revision as of 10:29, 9 March 2016

cGAS complexed with dsDNA (Based on PDB 4O6A)
cGAS-cGAMP-STING pathway

Cyclic GMP-AMP synthase (cGAS, cGAMP synthase), belonging to the nucleotidyltransferase family, is a cytosolic DNA sensor that activates the type-I interferon 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 were more vulnerable to lethal infection by DNA viruses.[5] In addition, cGAS has been shown to be an innate immune sensor of retroviruses including HIV.[6][7]

References

  1. ^ Sun, L; Wu, J; Du, F; Chen, X; Chen, ZJ (Dec 20, 2012). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 339 (6121): 786–91. doi:10.1126/science.1232458. PMID 23258413.
  2. ^ Wu, J; Sun, L; Chen, X; Du, F; Shi, H; Chen, C; Chen, ZJ (Dec 20, 2012). "Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA". Science. 339 (6121): 826–30. doi:10.1126/science.1229963. PMID 23258412.
  3. ^ Gao, Pu; Ascano, Manuel; Wu, Yang; Barchet, Winfried; Gaffney, Barbara L.; Zillinger, Thomas; Serganov, Artem A.; Liu, Yizhou; Jones, Roger A.; Hartmann, Gunther; Tuschl, Thomas; Patel, Dinshaw J. (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): 1094–1107. doi:10.1016/j.cell.2013.04.046. ISSN 0092-8674.
  4. ^ Zhang, X; Shi, H; Wu, J; Zhang, X; Sun, L; Chen, C; Chen, ZJ (Jun 3, 2013). "Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING". Molecular Cell. 51 (2): 226–235. doi:10.1016/j.molcel.2013.05.022.
  5. ^ Li, XD; Wu, J; Gao, D; Wang, H; Sun, L; Chen, ZJ (Sep 20, 2013). "Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects". Science. 341 (6152): 1390–4. doi:10.1126/science.1244040. PMC 3863637. PMID 23989956.
  6. ^ Gao, D; Wu, J; Wu, YT; Du, F; Aroh, C; Yan, N; Sun, L; Chen, ZJ (Aug 23, 2013). "Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses". Science. 341 (6148): 903–6. doi:10.1126/science.1240933. PMC 3860819. PMID 23929945.
  7. ^ Lahaye, X; Satoh, T; Gentili, M; Cerboni, S; Conrad, C; Hurbain, I; El Marjou, A; Lacabaratz, C; Lelièvre, JD; Manel, N (Dec 12, 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.


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