title: cGAS-cGAMP-STING: The three musketeers of cytosolic DNA sensing and signaling.
abstract: Innate immunity is the first line of host defense against invading pathogens. The detection of aberrant nucleic acids which represent some conserved PAMPs triggers robust type I IFN-mediated innate immune responses. Host- or pathogen-derived cytosolic DNA binds and activates the DNA sensor cGAS, which synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent downstream signaling. Here, we highlight recent progress in cGAS-cGAMP-STING, the Three Musketeers of cytosolic DNA sensing and signaling, and their essential roles in infection, autoimmune diseases, and cancer. We also focus on the regulation of these critical signal components by variant host/pathogen proteins and update our understanding of this indispensable pathway to provide new insights for drug discovery. © 2016 IUBMB Life, 68(11):858-870, 2016.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.|Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Jianli
authors.identifier: 0000-0003-0100-1489
authors.initials: J
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.|Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. jiangzf@pku.edu.cn.|Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China. jiangzf@pku.edu.cn.|Peking-Tsinghua Center for Life Sciences, Beijing, China. jiangzf@pku.edu.cn.
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000502:physiology*; D009713:Nucleotidyltransferases / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D008565:Membrane Proteins; D009712:Nucleotides, Cyclic; D009713:Nucleotidyltransferases; C532857:STING1 protein, human; D000099197:STING Protein; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: STING; cGAMP; cGAS; cancer; infection; inflammation; type I IFNs