PMID: 17706453 Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.

PMID: 17706543,10759890 Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-¦ÊB transcription through the classical IKK pathway

PMID: 17706543,10759890 Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-¦ÊB transcription through the classical IKK pathway

PMID: 17706453 TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.

PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKKvar epsilon PMID: 17706453,12133833,17468758 Physical association between TANK and NEMO suggest that the canonical IKK complex and the IKK-related kinases may exist as a physically associated signaling complex responsible for phosphorylation of additional transcription factors PMID: 17706453 NEMO acts downstream of MAVS and RIG-I, and physically interacts with the TANK adapter to mediate recruitment of TBK1 and IKKvar epsilon to the RIG-I?MAVS complex.

PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon

PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon

PMID: 17706453,15367631,14679297,16914100 Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues PMID: 17706543 Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.

PMID: 17706453,15367631,14679297,16914100 Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues PMID: 17706543 Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.

PMID: 17706453,10082512 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 hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300

PMID: 17706453 Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.

PMID: 17706453,10082512 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 hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300

PMID: 17706453,10082512 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 hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300

PMID: 17706453,17395583 Inactive IRF-3 constitutively shuttles into and out of the nucleus, whereas phosphorylation-dependent association with CBP/p300 retains IRF-3 in the nucleus and induces transcription of IFN-¦Â and other genes

PMID: 17706542 NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon

PMID: 17706453,17047224 Inducible activation of canonical NF-¦ÊB signaling requires phosphorylation of the I¦ÊB inhibitor by the 700?900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKK¦Â, and a non-enzymatic regulatory subunit NF-¦ÊB Essential Modulator (NEMO) or IKK¦Ã PMID: 17706543 MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKK¦Â complex which phosphorylates the inhibitory subunit I¦ÊBalpha, resulting in the release of NF-¦ÊB and activation of proinflammatory gene transcription.

PMID: 17706543 MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKK¦Â complex which phosphorylates the inhibitory subunit I¦ÊBalpha, resulting in the release of NF-¦ÊB and activation of proinflammatory gene transcription.

PMID: 17706453 The structural and functional consequences of this phosphorylation remain to be determined, although it is suggested that IKKvar epsilon-dependent phosphorylation of STAT1 appears to guide the transcriptional machinery to a subset of ISGs required for the direct antiviral response, whereas the IKK-independent genes may function in regulating the IFN signaling required for integration of innate and adaptive immune systems.

PMID:17706453 TRIM25 alpha contains a RING-finger domain, a B box/coiled-coil domain and a SPRY domain and induces robust ubiquitination of the CARD domains of RIG-I. PMID: 17706453 The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.

PMID: 17706453 The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.

PMID: 17706453,16785313,16125763,16153868,16177806 The adaptor molecule providing a link between RIG-I sensing of incoming viral RNA and downstream activation events was independently elucidated as mitochondrial antiviral signaling adapter (MAVS), also known as (IPS-1/VISA/Cardif) PMID: 17706453,16177806 MAVS interacts with RIG-I and recruits IKKvar epsilon through its C-terminal region; knockdown by siRNA inhibited RIG-I-dependent antiviral responses

PMID: 17706453 TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.

PMID: 17706453,17047224 Inducible activation of canonical NF-¦ÊB signaling requires phosphorylation of the I¦ÊB inhibitor by the 700?900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKK¦Â, and a non-enzymatic regulatory subunit NF-¦ÊB Essential Modulator (NEMO) or IKK¦Ã

PMID: 17706453,10759890 Both TBK-1 and IKK epsilon interact with the TNF-receptor-associated factor (TRAF)-interacting protein/TRAF family member-associated NF-¦ÊB activator (I-TRAF/TANK) protein, a modulator of TNF alpha-induced NF-¦ÊB activation

PMID: 17706543,14560022 Associated Protein 1 (NAP1), a homologue of I-TRAF/TANK, has also been shown to directly interact with TBK-1 and IKK epsilon