气候变化领域集成服务门户(CCPortal): TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections

CCPortal

DOI	10.1073/pnas.2100225118
	TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections
	Yum S.; Li M.; Fang Y.; Chen Z.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	The induction of type I interferons through the transcription factor interferon regulatory factor 3 (IRF3) is considered a major outcome of stimulator of interferon genes (STING) activation that drives immune responses against DNA viruses and tumors. However, STING activation can also trigger other downstream pathways such as nuclear factor κB (NF-κB) signaling and autophagy, and the roles of interferon (IFN)-independent functions of STING in infectious diseases or cancer are not well understood. Here, we generated a STING mouse strain with a mutation (S365A) that disrupts IRF3 binding and therefore type I interferon induction but not NF-κB activation or autophagy induction. We also generated STING mice with mutations that disrupt the recruitment of TANK-binding kinase 1 (TBK1), which is important for both IRF3 and NF-κB activation but not autophagy induction (L373A or ΔCTT, which lacks the C-terminal tail). The STING-S365A mutant mice, but not L373A or ΔCTT mice, were still resistant to herpes simplex virus 1 (HSV-1) infections and mounted an antitumor response after cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) treatment despite the absence of STING-induced interferons. These results demonstrate that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	cGAS; Interferon; NF-κB; STING; TBK1
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179994
作者单位	Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9148, United States; Center for Inflammation Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9148, United States; HHMI, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9148, United States
推荐引用方式 GB/T 7714	Yum S.,Li M.,Fang Y.,et al. TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections[J],2021,118(14).
APA	Yum S.,Li M.,Fang Y.,&Chen Z.J..(2021).TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Yum S.,et al."TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).