dsRNA binds to MDA5 RIG-I/MDA5 interacts with IPS-1 K-63-linked polyubiquitination of RIG-I dsRNA binds to RIG-I PathwayStep6965 PathwayStep6951 PathwayStep6948 PathwayStep6920 PathwayStep6921 PathwayStep6922 PathwayStep6923 PathwayStep6933 PathwayStep6939 Negative regulators of RIG-I/MDA5 signaling RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 Pubmed15208624 Pubmed16214811 Pubmed17395582 Pubmed17683970 Pubmed17942531 Pubmed18701081 Pubmed18989317 RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. Functionally RIG-I and MDA5 positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. RIG-I is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas MDA5 is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription. Reactome Database ID Release 43168928 Reactome, http://www.reactome.org ReactomeREACT_25359 Reviewed: Kawai, T, Akira, S, 2010-10-30 TRAF3-dependent IRF activation pathway NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 TRAF6 mediated IRF7 activation TRAF6 mediated NF-kB activation