| First Author | Cai X | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 1 | Pages | 113606 |
| PubMed ID | 38127621 | Mgi Jnum | J:351131 |
| Mgi Id | MGI:7574037 | Doi | 10.1016/j.celrep.2023.113606 |
| Citation | Cai X, et al. (2023) Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKK. Cell Rep 43(1):113606 |
| abstractText | 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 IkappaB kinase epsilon (IKK). However, the regulation of IKK 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 IKK and catalyzes asparagine hydroxylation of IKK at Asn-254, Asn-700, and Asn-701, resulting in the suppression of IKK activation. FIH-mediated hydroxylation of IKK prevents IKK binding to TBK1 and TRAF3 and attenuates the cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex-catalyzed K63-linked polyubiquitination of IKK 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 IKK activation for IFN signaling and antiviral immune responses. |
