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IFR3 (interferon regulatory factor 3) is a key transcriptional regulator of type I interferon (IFN)-dependent immune responses. It plays a critical role in the innate immune response against DNA and RNA viruses. IFR3 regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. It acts as a more potent activator of the IFN-beta gene than the IFN-alpha gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. IFR3 is found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA, or toll-like receptor signaling. It is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Mutations in the gene can result in encephalopathy, acute, infection-induced, herpes-specific 7.
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