cGAS in action: Expanding roles in immunity and inflammation

被引：944

作者：

Ablasser, Andrea ^{[1
]}

Chen, Zhijian J. ^{[2
]}

机构：

[1] Ecole Polytech Fed Lausanne, Global Hlth Inst, CH-1015 Lausanne, Switzerland

[2] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dept Mol Biol, Ctr Inflammat Res, Dallas, TX 75390 USA

来源：

SCIENCE | 2019年 / 363卷 / 6431期

基金：

欧洲研究理事会; 瑞士国家科学基金会;

关键词：

CYCLIC GMP-AMP; AICARDI-GOUTIERES-SYNDROME; ENDOPLASMIC-RETICULUM STRESS; CGAS/STING-DEPENDENT INNATE; DNA SENSOR; ENDOGENOUS; 2ND-MESSENGER; EXONUCLEASE TREX1; I INTERFERONS; ACTIVATION; CELLS;

D O I：

10.1126/science.aat8657

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

DNA is highly immunogenic. It represents a key pathogen-associated molecular pattern (PAMP) during infection. Host DNA can, however, also act as a danger-associated molecular pattern (DAMP) and elicit strong inflammatory responses. The cGAS-STING pathway has emerged as a major pathway that detects intracellular DNA. Here, we highlight recent advances on how cGAS and STING mediate inflammatory responses and how these are regulated, allowing cells to readily respond to infections and noxious agents while avoiding the inappropriate sensing of self-DNA. A particular focus is placed on the role of cGAS in the context of sterile inflammatory conditions. Manipulating cGAS or STING may open the door for new therapeutic strategies for the treatment of acute and chronic inflammation relevant to many human diseases.

引用

页码：1055 / +

页数：10

共 114 条

[1]

Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP [J].

Ablasser, Andrea ;

Schmid-Burgk, Jonathan L. ;

Hemmerling, Inga ;

Horvath, Gabor L. ;

Schmidt, Tobias ;

Latz, Eicke ;

Hornung, Veit .

NATURE, 2013, 503 (7477) :530-+

[2]

cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING [J].

Ablasser, Andrea ;

Goldeck, Marion ;

Cavlar, Taner ;

Deimling, Tobias ;

Witte, Gregor ;

Roehl, Ingo ;

Hopfner, Karl-Peter ;

Ludwig, Janos ;

Hornung, Veit .

NATURE, 2013, 498 (7454) :380-+

[3]

Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection [J].

Aguirre, Sebastian ;

Luthra, Priya ;

Sanchez-Aparicio, Maria T. ;

Maestre, Ana M. ;

Patel, Jenish ;

Lamothe, Francise ;

Fredericks, Anthony C. ;

Tripathi, Shashank ;

Zhu, Tongtong ;

Pintado-Silva, Jessica ;

Webb, Laurence G. ;

Bernal-Rubio, Dabeiba ;

Solovyov, Alexander ;

Greenbaum, Benjamin ;

Simon, Viviana ;

Basler, Christopher F. ;

Mulder, Lubbertus C. F. ;

Garcia-Sastre, Adolfo ;

Fernandez-Sesma, Ana .

NATURE MICROBIOLOGY, 2017, 2 (05)

[4]

Inflammation-driven carcinogenesis is mediated through STING [J].

Ahn, Jeonghyun ;

Xia, Tianli ;

Konno, Hiroyasu ;

Konno, Keiko ;

Ruiz, Phillip ;

Barber, Glen N. .

NATURE COMMUNICATIONS, 2014, 5

[5]

STING manifests self DNA-dependent inflammatory disease [J].

Ahn, Jeonghyun ;

Gutman, Delia ;

Saijo, Shinobu ;

Barber, Glen N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (47) :19386-19391

[6]

Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus [J].

An, Jie ;

Durcan, Laura ;

Karr, Reynold M. ;

Briggs, Tracy A. ;

Rice, Gillian I. ;

Teal, Thomas H. ;

Woodward, Joshua J. ;

Elkon, Keith B. .

ARTHRITIS & RHEUMATOLOGY, 2017, 69 (04) :800-807

[7]

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders [J].

Andreeva, Liudmila ;

Hiller, Bjoern ;

Kostrewa, Dirk ;

Laessig, Charlotte ;

Mann, Carina C. de Oliveira ;

Drexler, David Jan ;

Maiser, Andreas ;

Gaidt, Moritz ;

Leonhardt, Heinrich ;

Hornung, Veit ;

Hopfner, Karl-Peter .

NATURE, 2017, 549 (7672) :394-+

[8]

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J].

Baker, Darren J. ;

Childs, Bennett G. ;

Durik, Matej ;

Wijers, Melinde E. ;

Sieben, Cynthia J. ;

Zhong, Jian ;

Saltness, Rachel A. ;

Jeganathan, Karthik B. ;

Verzosa, Grace Casaclang ;

Pezeshki, Abdulmohammad ;

Khazaie, Khashayarsha ;

Miller, Jordan D. ;

van Deursen, Jan M. .

NATURE, 2016, 530 (7589) :184-+

[9]

Chromosomal instability drives metastasis through a cytosolic DNA response [J].

Bakhoum, Samuel F. ;

Ngo, Bryan ;

Laughney, Ashley M. ;

Cavallo, Julie-Ann ;

Murphy, Charles J. ;

Ly, Peter ;

Shah, Pragya ;

Sriram, Roshan K. ;

Watkins, Thomas B. K. ;

Taunk, Neil K. ;

Duran, Mercedes ;

Pauli, Chantal ;

Shaw, Christine ;

Chadalavada, Kalyani ;

Rajasekhar, Vinagolu K. ;

Genovese, Giulio ;

Venkatesan, Subramanian ;

Birkbak, Nicolai J. ;

McGranahan, Nicholas ;

Lundquist, Mark ;

LaPlant, Quincey ;

Healey, John H. ;

Elemento, Olivier ;

Chung, Christine H. ;

Lee, Nancy Y. ;

Imielenski, Marcin ;

Nanjangud, Gouri ;

Pe'er, Dana ;

Cleveland, Don W. ;

Powell, Simon N. ;

Lammerding, Jan ;

Swanton, Charles ;

Cantley, Lewis C. .

NATURE, 2018, 553 (7689) :467-+

[10]

Viruses transfer the antiviral second messenger cGAMP between cells [J].

Bridgeman, A. ;

Maelfait, J. ;

Davenne, T. ;

Partridge, T. ;

Peng, Y. ;

Mayer, A. ;

Dong, T. ;

Kaever, V. ;

Borrow, P. ;

Rehwinkel, J. .

SCIENCE, 2015, 349 (6253) :1228-1232

← 1 2 3 4 5 6 7 8 9 10 →