IRF3 Protein, Human (His)

IRF3, a key transcriptional regulator, plays a critical role in orchestrating type I interferon (IFN)-dependent immune responses against DNA and RNA viruses. It regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes by binding to an interferon-stimulated response element in their promoters, exhibiting greater potency in activating the IFN-beta gene. In uninfected cells, IRF3 remains in an inactive form in the cytoplasm, but upon viral infection, recognition of double-stranded RNA or toll-like receptor signaling leads to its phosphorylation by IKBKE and TBK1 kinases. This phosphorylation induces a conformational change, promoting dimerization, nuclear localization, and association with CREB binding protein to form dsRNA-activated factor 1 (DRAF1). This complex activates the transcription of type I IFN and IFN-stimulated genes, driving both early and late phases of gene induction. In the absence of viral infection, IRF3 is maintained as a monomer in an autoinhibited state, and its liberation for DNA binding and dimerization, along with nuclear localization, follows phosphorylation by TBK1 and IKBKE. This phosphorylation occurs in response to viral RNA, cytosolic DNA, or bacterial lipopolysaccharide, initiating a cascade involving innate adapter proteins (MAVS, STING1, or TICAM1) and culminating in the activation of IRF3, which subsequently induces IFNs in the nucleus.