The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling

被引：799

作者：

Cai, Xin ^{[1
]}

Chiu, Yu-Hsin ^{[3
]}

Chen, Zhijian J. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[3] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

来源：

MOLECULAR CELL | 2014年 / 54卷 / 02期

关键词：

CYCLIC DI-GMP; INNATE IMMUNE-RESPONSE; AMP SYNTHASE; VIRUS TYPE-1; DENDRITIC CELLS; SENSOR CGAS; RECOGNITION; 2ND-MESSENGER; HIV-1; DINUCLEOTIDE;

D O I：

10.1016/j.molcel.2014.03.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The innate immune system deploys a variety of sensors to detect signs of infection. Nucleic acids represent a major class of pathogen signatures that can trigger robust immune responses. The presence of DNA in the cytoplasm of mammalian cells is a danger signal that activates innate immune responses; however, how cytosolic DNA triggers these responses remained unclear until recently. In this review, we focus on the mechanism of DNA sensing by the newly discovered cGAS-cGAMP-STING pathway and highlight recent progress in dissecting the in vivo functions of this pathway in immune defense as well as autoimmunity.

引用

页码：289 / 296

页数：8

共 63 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] 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

[4] STING and the innate immune response to nucleic acids in the cytosol [J].

Burdette, Dara L. ;

Vance, Russell E. .

NATURE IMMUNOLOGY, 2013, 14 (01) :19-26

[5] STING is a direct innate immune sensor of cyclic di-GMP [J].

Burdette, Dara L. ;

Monroe, Kathryn M. ;

Sotelo-Troha, Katia ;

Iwig, Jeff S. ;

Eckert, Barbara ;

Hyodo, Mamoru ;

Hayakawa, Yoshihiro ;

Vance, Russell E. .

NATURE, 2011, 478 (7370) :515-U111

[6] Structural mechanism of cytosolic DNA sensing by cGAS [J].

Civril, Filiz ;

Deimling, Tobias ;

Mann, Carina C. de Oliveira ;

Ablasser, Andrea ;

Moldt, Manuela ;

Witte, Gregor ;

Hornung, Veit ;

Hopfner, Karl-Peter .

NATURE, 2013, 498 (7454) :332-+

[7] Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus [J].

Crow, Yanick J. ;

Hayward, Bruce E. ;

Parmar, Rekha ;

Robins, Peter ;

Leitch, Andrea ;

Ali, Manir ;

Black, Deborah N. ;

van Bokhoven, Hans ;

Brunner, Han G. ;

Hamel, Ben C. ;

Corry, Peter C. ;

Cowan, Frances M. ;

Frints, Suzanne G. ;

Klepper, Joerg ;

Livingston, John H. ;

Lynch, Sally Ann ;

Massey, Roger F. ;

Meritet, Jean Francois ;

Michaud, Jacques L. ;

Ponsot, Gerard ;

Voit, Thomas ;

Lebon, Pierre ;

Bonthron, David T. ;

Jackson, Andrew P. ;

Barnes, Deborah E. ;

Lindahl, Tomas .

NATURE GENETICS, 2006, 38 (08) :917-920

[8] The Innate Immune DNA Sensor cGAS Produces a Noncanonical Cyclic Dinucleotide that Activates Human STING [J].

Diner, Elie J. ;

Burdette, Dara L. ;

Wilson, Stephen C. ;

Monroe, Kathryn M. ;

Kellenberger, Colleen A. ;

Hyodo, Mamoru ;

Hayakawa, Yoshihiro ;

Hammond, Ming C. ;

Vance, Russell E. .

CELL REPORTS, 2013, 3 (05) :1355-1361

[9] Autoimmunity Initiates in Nonhematopoietic Cells and Progresses via Lymphocytes in an Interferon-Dependent Autoimmune Disease [J].

Gall, Alevtina ;

Treuting, Piper ;

Elkon, Keith B. ;

Loo, Yueh-Ming ;

Gale, Michael, Jr. ;

Barber, Glen N. ;

Stetson, Daniel B. .

IMMUNITY, 2012, 36 (01) :120-131

[10] Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses [J].

Gao, Daxing ;

Wu, Jiaxi ;

Wu, You-Tong ;

Du, Fenghe ;

Aroh, Chukwuemika ;

Yan, Nan ;

Sun, Lijun ;

Chen, Zhijian J. .

SCIENCE, 2013, 341 (6148) :903-906

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