PUBLICATION
Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKKϵ
- Authors
- Cai, X., Wang, R., Zhu, J., Li, X., Liu, X., Ouyang, G., Wang, J., Li, Z., Zhu, C., Deng, H., Xiao, W.
- ID
- ZDB-PUB-231222-3
- Date
- 2023
- Source
- Cell Reports 43: 113606113606 (Journal)
- Registered Authors
- Li, Xiong, Li, Zhi, Ouyang, Gang, Wang, Jing, Xiao, Wuhan
- Keywords
- CP: Immunology, FIH, IKKϵ, MAVS, TBK1, TRAF3, hydroxylation, hypoxia, innate immunity, mouse, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Hydroxylation
- I-kappa B Kinase*/metabolism
- Immunity, Innate
- Mice
- Repressor Proteins/metabolism
- Virus Diseases*
- Zebrafish/metabolism
- PubMed
- 38127621 Full text @ Cell Rep.
Citation
Cai, X., Wang, R., Zhu, J., Li, X., Liu, X., Ouyang, G., Wang, J., Li, Z., Zhu, C., Deng, H., Xiao, W. (2023) Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKKϵ. Cell Reports. 43:113606113606.
Abstract
Activation of type I interferon (IFN-1) signaling is essential to protect host cells from viral infection. The full spectrum of IFN-I induction requires the activation of a number of cellular factors, including IκB kinase epsilon (IKKϵ). However, the regulation of IKKϵ activation in response to viral infection remains largely unknown. Here, we show that factor inhibiting hypoxia-inducible factor (HIF) (FIH), an asparaginyl hydroxylase, interacts with IKKϵ and catalyzes asparagine hydroxylation of IKKϵ at Asn-254, Asn-700, and Asn-701, resulting in the suppression of IKKϵ activation. FIH-mediated hydroxylation of IKKϵ prevents IKKϵ binding to TBK1 and TRAF3 and attenuates the cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex-catalyzed K63-linked polyubiquitination of IKKϵ at Lys-416. In addition, Fih-deficient mice and zebrafish are more resistant to viral infection. This work uncovers a previously unrecognized role of FIH in suppressing IKKϵ activation for IFN signaling and antiviral immune responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping