Open AccessG3BP1 promotes DNA binding and activation of cGAS
Author(s) -
Zhao-Shan Liu,
Hong Cai,
Wei Xue,
Miao Wang,
Tian Xia,
Wan-Jin Li,
Jia-Qing Xing,
Ming Zhao,
Yanhong Huang,
Shuai Chen,
Shengming Wu,
Xinzheng Wang,
Xin Liu,
Xue Pang,
Ziyu Zhang,
Tingting Li,
Jiang Dai,
Fangting Dong,
Qing Xia,
Ailing Li,
Tao Zhou,
Zheng-gang Liu,
Xuemin Zhang,
Tao Li
Publication year - 2018
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-018-0262-4
Subject(s) - dna , stress granule , microbiology and biotechnology , biology , chemistry , gene , biochemistry , messenger rna , translation (biology)
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-Goutières 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.