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19.7894 c 4.9886 3.3337 -3.7283 14.915 -7.5982 13.3243 c 7.1844 -7.6993 6.2238 4.1184 -0.0987 -9.7867 l 26.2042 -12.6627 c 4.875 -3.4821 13.7627 7.9809 10.9766 10.9902 z" style="fill:url(#MO_6aef48);stroke:none;"/> </svg> indirect PMID: 17395583, 9463386, 12692549, 9566918, 12702806 Transcriptional activity of IRF-3 is controlled by virus and dsRNA-induced, C-terminal phosphorylation events on serines 385 and 386, as well as the serine/threonine cluster between amino acids 396 and 405, mediated by the IKK-related kinases TBK-1 and IKK{epsilon} indirect PMID: 17395583, 9463386, 12692549, 9566918, 12702806 Transcriptional activity of IRF-3 is controlled by virus and dsRNA-induced, C-terminal phosphorylation events on serines 385 and 386, as well as the serine/threonine cluster between amino acids 396 and 405, mediated by the IKK-related kinases TBK-1 and IKK{epsilon} PMID: 17395583, 10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and heterodimerization, nuclear localization, and association with the co-activator CBP/p300. PMID: 17395583, 10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and heterodimerization, nuclear localization, and association with the co-activator CBP/p300. PMID: 17395583, 10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and heterodimerization, nuclear localization, and association with the co-activator CBP/p300. PMID: 17395583, 10082512 Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and heterodimerization, nuclear localization, and association with the co-activator CBP/p300. PMID: 17395583, 10805757 phosphorylation-dependent association with CBP/p300 retains IRF-3 in the nucleus and induces transcription of IFN-beta and other genes. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583 IRF-3 possesses a restricted DNA binding site specificity and interacts with CBP. PMID: 17395583, 10805757 phosphorylation-dependent association with CBP/p300 retains IRF-3 in the nucleus and induces transcription of IFN-beta and other genes. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 10805757 Inactive IRF-3 constitutively shuttles into and out of the nucleus PMID: 17395583, 10805757 Inactive IRF-3 constitutively shuttles into and out of the nucleus PMID: 17395583, 12692549, 12702806 An important breakthrough in the understanding of innate immune response signaling was the demonstration that IRF-3 and IRF-7 are the primary in vivo targets of the IKK-related kinases, TBK-1/NAK/T2K and IKK{epsilon}/IKKi. PMID: 17395583, 15367631, 14679297 Both kinases directly phosphorylate IRF-3 and IRF-7 in their C-terminal signal-responsive domain PMID: 17395583, 12692549, 12702806 An important breakthrough in the understanding of innate immune response signaling was the demonstration that IRF-3 and IRF-7 are the primary in vivo targets of the IKK-related kinases, TBK-1/NAK/T2K and IKK{epsilon}/IKKi. PMID: 17395583, 15367631, 14679297 Both kinases directly phosphorylate IRF-3 and IRF-7 in their C-terminal signal-responsive domain indirect PMID: 17395583, 10924517 IFN and lipopolysaccharide treatment modulates transcription of the IRF-7 gene. indirect PMID: 17395583, 10924517 IFN and lipopolysaccharide treatment modulates transcription of the IRF-7 gene. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 10938111 Human IFN-beta, IFN-{alpha}1, and RANTES (regulated on activation normal T cell expressed and secreted) promoters are stimulated by IRF-3 coexpression, whereas IFN-{alpha}4, -{alpha}7, and -{alpha}14 promoters are preferentially induced by IRF-7 only. PMID: 17395583, 17015689 IRF-3 is recruited to Cullin1 following virus infection, and expression of a dominant-negative Cullin1 inhibits IRF-3 degradation. PMID: 17395583, 17015689, 9566918 IRF-3 is targeted for proteasomal degradation (9) following virus infection, and polyubiquitination is required for IRF-3 degradation. PMID: 17395583 After stimulation by dsRNA, phosphorylation of the Ser339–Pro340 motif of IRF-3 results in the interaction with Pin1, polyubiquitination, and then proteasome-dependent degradation of IRF-3 PMID: 17395583 After stimulation by dsRNA, phosphorylation of the Ser339–Pro340 motif of IRF-3 results in the interaction with Pin1, polyubiquitination, and then proteasome-dependent degradation of IRF-3 PMID: 17395583 ISGylation subverts ubiquitin-mediated degradation of IRF-3 and enhances IRF-3-dependent gene activity PMID: 17395583 After stimulation by dsRNA, phosphorylation of the Ser339–Pro340 motif of IRF-3 results in the interaction with Pin1, polyubiquitination, and then proteasome-dependent degradation of IRF-3 PMID: 17395583 IRF-3 can also be stabilized in infected cells; both IFN treatment and RNA virus infection increase conjugation of the IFN-induced, ubiquitin-like protein ISG15 to IRF-3. PMID: 17395583, 15208624, 15563593 Antiviral immune responses can be triggered by dsRNA and the 5'-triphosphate RNA structure of viral nucleic acids.These structures are "sensed" by the cytoplasmic RNA helicase proteins RIG-I and MDA5 PMID: 17395583, 15208624, 15563593 Antiviral immune responses can be triggered by dsRNA and the 5'-triphosphate RNA structure of viral nucleic acids.These structures are "sensed" by the cytoplasmic RNA helicase proteins RIG-I and MDA5 PMID: 17395583, 16177806, 16153868, 16125763, 16127453, 15563593 The protein responsible for downstream signaling is a mitochondrial adapter, known as MAVS/IPS-1/ VISA/Cardif that interacts with RIG-I via CARD domain interactions. PMID: 17395583, 16177806, 16153868, 16125763, 16127453, 15563593 The protein responsible for downstream signaling is a mitochondrial adapter, known as MAVS/IPS-1/ VISA/Cardif that interacts with RIG-I via CARD domain interactions. PMID: 17395583, 17190814 LGP2 was shown to interact directly with RIG-I to block RIG-I dimerization and downstream signaling to the IFN response. PMID: 17395583 MAVS links RIG-I and MDA5 to TRAF3. PMID: 17395583 MAVS links RIG-I and MDA5 to TRAF3. PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. indirect PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. indirect PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. indirect PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. indirect PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. PMID: 17395583 TRAF-dependent induction of the kinases JNK, IKK{alpha}, IKKbeta, IKK{epsilon}, TBK-1, and IRAK1 induce the binding of ATF2-c-Jun, NF-{kappa}B (p50-p65 complex), IRF-3, and IRF-7 to sequence-specific PRDs located in the IFN-beta enhancer. PMID: 17395583 Coordinated assembly of these factors forms the IFN-beta enhanceosome, which is responsible for the transcriptional induction of this antiviral cytokine. PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. indirect PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. indirect PMID: 17395583 Viral pathogen-associated molecular patterns trigger multiple signaling cascades through Toll-like receptor-dependent (TLR-3, TLR-7, and TLR-9) and -independent (RIG-I and MDA5) pathways leading to kinase activation through TRAF family members. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. indirect PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. indirect PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment. PMID: 17395583 In plasmacytoid dendritic cells, TLR-7 or TLR-9 engagement leads to direct activation of IRF-7 through MyD88/TRAF6/IRAK4/IRAK1 recruitment.