Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The i...Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The identification of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP)synthase(cGAS)as a major cytosolic DNA receptor is a milestone in the field of DNA sensing.The engagement of cGAS by double-stranded DNA from different origins,including invading pathogens,damaged mitochondria,ruptured micronuclei,and genomic DNA results in the generation of cGAMP and activation of stimulator of interferon genes,which thereby activates innate immunity mainly characterized by the activation of type I interferon response.In recent years,great progress has been made in understanding the subcellular localization and novel functions of cGAS.In this review,we particularlyfocus on summarizingthe multifaceted roles ofcGAS in regulating senescence,autophagy,cell stemness,apoptosis,angiogenesis,cell proliferation,antitumor effect,DNA replication,DNA damage repair,micronucleophagy,as well as cell metabolism.展开更多
基金This work was supported by the National Natural Science Foundation of China(81922030 and 81770006 to H.L,32188101,32030038,91842303,and 31730025 to B.G.)the Major Research Plan of National Natural Science Foundation of China(2017YFA0505900 to B.G.),Shanghai Shu Guang Program(205G19)Shanghai Science and Technology Fund(19140900600 and 22S11900700 to H.L.).
文摘Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The identification of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP)synthase(cGAS)as a major cytosolic DNA receptor is a milestone in the field of DNA sensing.The engagement of cGAS by double-stranded DNA from different origins,including invading pathogens,damaged mitochondria,ruptured micronuclei,and genomic DNA results in the generation of cGAMP and activation of stimulator of interferon genes,which thereby activates innate immunity mainly characterized by the activation of type I interferon response.In recent years,great progress has been made in understanding the subcellular localization and novel functions of cGAS.In this review,we particularlyfocus on summarizingthe multifaceted roles ofcGAS in regulating senescence,autophagy,cell stemness,apoptosis,angiogenesis,cell proliferation,antitumor effect,DNA replication,DNA damage repair,micronucleophagy,as well as cell metabolism.
