G3BP1 promotes DNA binding and activation of cGAS

Liu Zhao-Shan; Cai Hong; Xue Wen; Wang Miao; Xia Tian; Li Wan-Jin; Xing Jia-Qing; Zhao Ming; Huang Yi-Jiao; Chen Shuai; Wu Sheng-Ming; Wang Xinzheng; Liu Xin; Pang Xue; Zhang Zi-Yu; Li Tingting; Dai Jiang; Dong Fangting; Xia Qing; Li Ai-Ling; Zhou Tao; Liu Zheng-gang; Zhang Xue-Min; Li Tao

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G3BP1 promotes DNA binding and activation of cGAS

机译：G3bp1促进了CGA的DNA结合和活化

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Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutieres syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.

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来源
《Nature immunology》 |2019年第1期|共13页
作者
Liu Zhao-Shan; Cai Hong; Xue Wen; Wang Miao; Xia Tian; Li Wan-Jin; Xing Jia-Qing; Zhao Ming; Huang Yi-Jiao; Chen Shuai; Wu Sheng-Ming; Wang Xinzheng; Liu Xin; Pang Xue; Zhang Zi-Yu; Li Tingting; Dai Jiang; Dong Fangting; Xia Qing; Li Ai-Ling; Zhou Tao; Liu Zheng-gang; Zhang Xue-Min; Li Tao;
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作者单位

Natl Ctr Biomed Anal Inst Pharmacol &

Toxicol State Key Lab Toxicol &

Med Countermeasures;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Pharmacol &

Toxicol State Key Lab Toxicol &

Med Countermeasures;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

Natl Ctr Biomed Anal Inst Basic Med Sci State Key Lab Prote Beijing Peoples R China;

NCI Ctr Canc Res NIH Bethesda MD 20892 USA;

Natl Ctr Biomed Anal Inst Pharmacol &

Toxicol State Key Lab Toxicol &

Med Countermeasures;

Natl Ctr Biomed Anal Inst Pharmacol &

Toxicol State Key Lab Toxicol &

Med Countermeasures;

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正文语种 eng
中图分类医学免疫学;
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G3BP1 promotes DNA binding and activation of cGAS

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