Non-Canonical Role of IKK? in the Regulation of STAT1 Phosphorylation in Antiviral Signaling.

ABSTRACT: Non-self RNA is recognized by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), inducing type I interferons (IFNs). Type I IFN promotes the expression of IFN-stimulated genes (ISGs), which requires the activation of signal transducer and activator of transcription-1 (STAT1). We previously reported that dsRNA induced STAT1 phosphorylation via a type I IFN-independent pathway in addition to the well-known type I IFN-dependent pathway. I?B kinase ? (IKK?) is involved in antiviral signaling induced by dsRNA; however, its role is incompletely understood. Here, we explored the function of IKK? in RLR-mediated STAT1 phosphorylation. Silencing of IKK? markedly decreased the level of IFN-? and STAT1 phosphorylation inHeH response to dsRNA. However, the inhibition of IKK? did not alter the RLR signaling-mediated dimerization of interferon responsive factor 3 (IRF3) or the nuclear translocation of nuclear factor-?B (NF?B). These results suggest a non-canonical role of IKK? in RLR signaling. Furthermore, phosphorylation of STAT1 was suppressed by IKK? knockdown in cells treated with a specific neutralizing antibody for the type I IFN receptor (IFNAR) and in IFNAR-deficient cells. Collectively, the dual regulation of STAT1 by IKK? in antiviral signaling suggests a role for IKK? in the fine-tuning of antiviral signaling in response to non-self RNA.

SUBMITTER: Xing F 

PROVIDER: S-EPMC5167405 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature