Open AccessTBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections
Author(s) -
Seoyun Yum,
Minghao Li,
Fang Yan,
Zhijian J. Chen
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100225118
Subject(s) - irf3 , sting , tank binding kinase 1 , immune system , stimulator of interferon genes , biology , signal transduction , interferon regulatory factors , immunology , cancer research , innate immune system , microbiology and biotechnology , mitogen activated protein kinase kinase , engineering , aerospace engineering , protein kinase c
Significance The cGAS-STING pathway is important for immune defense against infection and cancer. STING activation triggers multiple signaling cascades leading to activation of IRF3, NF-κB, and autophagy. By generating mice harboring mutations of STING that specifically inactivate different signaling cascades, we found that ablation of IRF3 activation, which is essential for the induction of type I interferons, was not sufficient to abolish the immune defense against virus infection and cancer in mouse models. Rather, impairing the ability of STING to recruit TBK1, which is important for activating both IRF3 and NF-κB, abolished the immune defense functions of STING. These results demonstrate that the recruitment of TBK1 to STING has functions that are broader than activating IRF3 and inducing type I interferons.