IRF3
Description
The IRF3 (interferon regulatory factor 3) is a protein-coding gene located on chromosome 19.
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.
== Function == IRF3 is a member of the interferon regulatory transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites. IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. The complex translocates into the nucleus for the transcriptional activation of interferons alpha and beta, and further interferon-induced genes. IRF3 plays an important role in the innate immune system's response to viral infection. Aggregated MAVS have been found to activate IRF3 dimerization. A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons. Another study has shown that IRF3-/- knockouts protect from myocardial infarction. The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-myocardial infarction cardioprotection.
IRF3 is a key transcription factor that plays a crucial role in the innate immune response against DNA and RNA viruses by regulating the production of type I interferons (IFN-alpha and IFN-beta) and interferon-stimulated genes (ISGs). It binds to an interferon-stimulated response element (ISRE) in the promoters of these genes, activating their transcription. IRF3 is a more potent activator of the IFN-beta gene than the IFN-alpha gene and is critical in both the early and late phases of IFN-alpha/beta gene induction. In uninfected cells, IRF3 exists in an inactive form in the cytoplasm. Upon viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, IRF3 is phosphorylated by IKBKE and TBK1 kinases, leading to a conformational change. This triggers its dimerization and translocation into the nucleus, where it associates with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1). This complex then activates the transcription of type I IFN and ISG genes. IRF3 can also activate distinct gene expression programs in macrophages and induce apoptosis in primary macrophages. In response to Sendai virus infection, IRF3 is recruited to mitochondria by TOMM70:HSP90AA1, forming an apoptosis complex (TOMM70:HSP90AA1:IRF3:BAX) that triggers apoptosis. IRF3 is also a key transcription factor regulating the IFN response during SARS-CoV-2 infection.
IRF3 is also known as IIAE7.
