Human Interferon Regulatory Factor 3, IRF3 ELI

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 (PubMed: 22394562, PubMed: 25636800, PubMed: 27302953).

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 (PubMed: 11846977, PubMed: 16846591, PubMed: 16979567, PubMed: 20049431, PubMed: 32972995).

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 (PubMed: 16846591, PubMed: 16979567, PubMed: 20049431).

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 (PubMed: 22394562, PubMed: 25636800, PubMed: 27302953).

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 (PubMed: 16154084, PubMed: 27302953, PubMed: 33440148).

Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed: 16846591).

In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed: 25609812).

Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed: 33440148).