IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminalDNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist.[1]
Clinical significance
IRF5 acts as a molecular switch that controls whether macrophages will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."[2]
↑Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA (January 2011). "IRF5 promotes inflammatory macrophage polarization and T(H)1-T(H)17 responses". Nat Immunol. 12 (3): 231–238. doi:10.1038/ni.1990. PMID21240265. Lay summary – MedScape.
Further reading
Pitha PM, Au WC, Lowther W, et al. (1999). "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie. 80 (8–9): 651–8. doi:10.1016/S0300-9084(99)80018-2. PMID9865487.
Barnes B, Lubyova B, Pitha PM (2002). "On the role of IRF in host defense". J. Interferon Cytokine Res. 22 (1): 59–71. doi:10.1089/107999002753452665. PMID11846976.
Barnes BJ, Moore PA, Pitha PM (2001). "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. doi:10.1074/jbc.M101216200. PMID11303025.
Barnes BJ, Field AE, Pitha-Rowe PM (2003). "Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes". J. Biol. Chem. 278 (19): 16630–41. doi:10.1074/jbc.M212609200. PMID12600985.
Barnes BJ, Kellum MJ, Pinder KE, et al. (2003). "Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death". Cancer Res. 63 (19): 6424–31. PMID14559832.
Barnes BJ, Richards J, Mancl M, et al. (2004). "Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection". J. Biol. Chem. 279 (43): 45194–207. doi:10.1074/jbc.M400726200. PMID15308637.
Lin R, Yang L, Arguello M, et al. (2005). "A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization". J. Biol. Chem. 280 (4): 3088–95. doi:10.1074/jbc.M408452200. PMID15556946.
Takaoka A, Yanai H, Kondo S, et al. (2005). "Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors". Nature. 434 (7030): 243–9. doi:10.1038/nature03308. PMID15665823.
Schoenemeyer A, Barnes BJ, Mancl ME, et al. (2005). "The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling". J. Biol. Chem. 280 (17): 17005–12. doi:10.1074/jbc.M412584200. PMID15695821.
Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K, Fitzgerald-Bocarsly P, Pitha PM, Pinder K, Barnes BJ (June 2005). "Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function". J. Biol. Chem. 280 (22): 21078–90. doi:10.1074/jbc.M500543200. PMID15805103.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
Graham RR, Kozyrev SV, Baechler EC, et al. (2006). "A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus". Nat. Genet. 38 (5): 550–5. doi:10.1038/ng1782. PMID16642019.