Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (   ). 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 (   ). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction ( , ). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, 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 (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes ( , ). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages . In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis . Key transcription factor regulating the IFN response during SARS-CoV-2 infection .
Subcellular locations: Cytoplasm, Nucleus, Mitochondrion
Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect (, ). When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm . Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection .
Expressed constitutively in a variety of tissues.