Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKKϵ.
Cell Rep
; 43(1): 113606, 2024 01 23.
Article
en En
| MEDLINE
| ID: mdl-38127621
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.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Virosis
/
Quinasa I-kappa B
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article