p-T,4S-IRF3 is dimerized Phosphorylation and release of IRF3 Dimerized phospho-IRF3 migrates to the nucleus Recruitment of IRF3 to activated DAI:TBK1 Recruitment TBK1 to dsDNA:DAI followed by its activation PathwayStep6994 PathwayStep6993 PathwayStep6992 PathwayStep6991 PathwayStep6990 IRF3 mediated activation of type 1 IFN Authored: Shamovsky, V, 2011-09-21 Edited: Shamovsky, V, 2012-02-23 Interferon regulatory factors (IRF) IRF-3 and IRF-7 are the major modulators of IFN gene expression in response to pathogenic molecules. The relative contribution of IRF3 and IRF7 depends on the signaling pathway that is activated. Type I IFN production in cytosolic DNA-sensing pathway is mediated predominantly by IRF3 and partially by IRF7, since DNA-stimulated IFN-beta and IFN-alpha4 mRNA induction was strongly inhibited in IRF3-deficient mouse embryonic fibroblasts (MEFs), while remained normal (IFN-beta) or reduced (IFN-alpha4) in IRF7-deficient MEFs (Takaoke A et al 2007). IRF3 activation in response to B-DNA stimulation occurs via its co-recruitment with serine/threonine kinase TANK-binding kinase 1 (TBK1) or inducible IkB kinase (IKKi/IKKepsilon) to the C-terminal region of DAI. Pubmed16413926 Pubmed17618271 Pubmed18375758 Pubmed19846511 Reactome Database ID Release 431606341 Reactome, http://www.reactome.org ReactomeREACT_118811 Reviewed: D'Eustachio, P, 2011-12-07 Reviewed: Upton, JW, Mocarski, ES, 2012--0-2-