Aerospace engineering

TANK-binding kinase 1

Autophagy

Sting

IRF3

Biology

Engineering

Innate immune system

Apoptosis

Protein kinase C

Immunology

Stimulator of interferon genes

Signal transduction

Mitogen-activated protein kinase kinase

Cell biology

Cancer research

Genetics

Immune system

Interferon regulatory factors

Proceedings of the National Academy of Sciences

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.

TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections