Biology:IRF3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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.

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

IRF3 has been shown to interact with IRF7.

Further reading

• "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie 80 (8–9): 651–8. 1999. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487. 
• "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. 2002. doi:10.1089/107999002753452674. PMID 11846977. 
• "Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes". Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11657–61. 1996. doi:10.1073/pnas.92.25.11657. PMID 8524823. 
• "Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300". EMBO J. 17 (4): 1087–95. 1998. doi:10.1093/emboj/17.4.1087. PMID 9463386. 
• "Interferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1". Mol. Cell. Biol. 18 (3): 1359–68. 1998. doi:10.1128/MCB.18.3.1359. PMID 9488451. 
• "Virus-Dependent Phosphorylation of the IRF-3 Transcription Factor Regulates Nuclear Translocation, Transactivation Potential, and Proteasome-Mediated Degradation". Mol. Cell. Biol. 18 (5): 2986–96. 1998. doi:10.1128/MCB.18.5.2986. PMID 9566918. 
• "Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity". Genes Dev. 12 (13): 2061–72. 1998. doi:10.1101/gad.12.13.2061. PMID 9649509. 
• "Mapping of human interferon regulatory factor 3 (IRF3) to chromosome 19q13.3-13.4 by an intragenic polymorphic marker". Annals of Human Genetics 62 (Pt 3): 231–4. 1999. doi:10.1046/j.1469-1809.1998.6230231.x. PMID 9803267. 
• "Cloning and functional analysis of the human IRF-3 promoter". DNA Cell Biol. 18 (9): 685–92. 1999. doi:10.1089/104454999314962. PMID 10492399. 
• "Activation of interferon regulatory factor 3 in response to DNA-damaging agents". J. Biol. Chem. 274 (43): 30686–9. 1999. doi:10.1074/jbc.274.43.30686. PMID 10521456. 
• "Regulated Nuclear-Cytoplasmic Localization of Interferon Regulatory Factor 3, a Subunit of Double-Stranded RNA-Activated Factor 1". Mol. Cell. Biol. 20 (11): 4159–68. 2000. doi:10.1128/MCB.20.11.4159-4168.2000. PMID 10805757. 
• "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7. 2000. doi:10.1093/oxfordjournals.jbchem.a022753. PMID 10920266. 
• "Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3". J. Biol. Chem. 276 (1): 355–63. 2001. doi:10.1074/jbc.M007790200. PMID 11035028. 
• "IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein". J. Biol. Chem. 276 (12): 8951–7. 2001. doi:10.1074/jbc.M008717200. PMID 11124948. 
• "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology 280 (2): 273–82. 2001. doi:10.1006/viro.2000.0782. PMID 11162841. 
• "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes". J. Biol. Chem. 276 (26): 23382–90. 2001. doi:10.1074/jbc.M101216200. PMID 11303025. 
• "The Small RNA gene activator protein, SphI postoctamer homology-binding factor/selenocysteine tRNA gene transcription activating factor, stimulates transcription of the human interferon regulatory factor-3 gene". J. Biol. Chem. 277 (7): 4853–8. 2002. doi:10.1074/jbc.M108308200. PMID 11724783. 
• "Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription". J. Mol. Biol. 316 (5): 1009–22. 2002. doi:10.1006/jmbi.2001.5401. PMID 11884139. 
• "Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3 by lipopolysaccharide". Journal of Immunology 172 (2): 747–51. 2004. doi:10.4049/jimmunol.172.2.747. PMID 14707042. 

External links

• Interferon+Regulatory+Factor-3 at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook IRF3