PMID: 18549796 The ligands for RIG-I and MDA-5 are viral ¡Ènonself¡É nucleic acids, and like TLR signaling, a classical ligand-receptor-adaptor model of PRR signaling has been proposed for RLH-mediated signaling, culminating in the induction of antiviral type-1 interferon cytokines, such as IFN-¦Â and IFN-¦Á.

PMID: 18549796, 18272355 The MAVS proline-rich domain contains a TRAF3-binding site required for association with TRAF3 and essential for MAVS-mediated activation of type-1 interferon, but not NF-¦ÊB. PMID: 18549796 The deubiquitinizing enzyme A (DUBA) cleaves Lys-63-linked polyubiquitin chains from TRAF3 resulting in the dissociation of TRAF3 from TBK1, and such a dissociation effectively squelches RLH-mediated type-1 interferon production.

PMID: 18549796, 16153868 Conversely, mutation of a MAVS TRAF6-binding site showed marked reduction in MAVS-mediated NF-¦ÊB activity, suggesting that TRAF6 mediates MAVS activation of NF-¦ÊB.

PMID: 18549796 MAVS signaling downstream of TRAF6 is thought to involve the activation of the canonical I¦ÊB kinase (IKK) complex consisting of IKK¦Ã(NEMO):IKK¦Á:IKK¦Â, resulting in the phosphorylation of the inhibitor of NF-¦ÊB (I¦ÊB¦Á) and its subsequent release for translocation into the nucleus.

PMID: 18549796 MAVS signaling downstream of TRAF6 is thought to involve the activation of the canonical I¦ÊB kinase (IKK) complex consisting of IKK¦Ã(NEMO):IKK¦Á:IKK¦Â, resulting in the phosphorylation of the inhibitor of NF-¦ÊB (I¦ÊB¦Á) and its subsequent release for translocation into the nucleus.

PMID: 18549796 MAVS signaling downstream of TRAF6 is thought to involve the activation of the canonical I¦ÊB kinase (IKK) complex consisting of IKK¦Ã(NEMO):IKK¦Á:IKK¦Â, resulting in the phosphorylation of the inhibitor of NF-¦ÊB (I¦ÊB¦Á) and its subsequent release for translocation into the nucleus.

PMID: 18549796 MAVS signaling downstream of TRAF6 is thought to involve the activation of the canonical I¦ÊB kinase (IKK) complex consisting of IKK¦Ã(NEMO):IKK¦Á:IKK¦Â, resulting in the phosphorylation of the inhibitor of NF-¦ÊB (I¦ÊB¦Á) and its subsequent release for translocation into the nucleus.

PMID: 18549796 In contrast, MAVS signaling downstream of TRAF3 involves the formation and activation of a different signaling complex consisting of MAVS, the TRAF-family-member-associated NF-¦ÊB activator (TANK), and a noncanonical class of IKKs including (TANK)-binding kinase 1 (TBK1) and inducible I¦ÊB kinase (IKK-? or IKK-var epsilon). PMID: 18549796 The deubiquitinizing enzyme A (DUBA) cleaves Lys-63-linked polyubiquitin chains from TRAF3 resulting in the dissociation of TRAF3 from TBK1, and such a dissociation effectively squelches RLH-mediated type-1 interferon production.

PMID: 18549796 In contrast, MAVS signaling downstream of TRAF3 involves the formation and activation of a different signaling complex consisting of MAVS, the TRAF-family-member-associated NF-¦ÊB activator (TANK), and a noncanonical class of IKKs including (TANK)-binding kinase 1 (TBK1) and inducible I¦ÊB kinase (IKK-? or IKK-var epsilon).

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7. PMID: 18549796, 17079289 NS1 was found to complex with RIG-I and associate with MAVS at the mitochondria, thereby disrupting downstream activation of IRF-3.

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7.

PMID: 18549796 The ligands for RIG-I and MDA-5 are viral ¡Ènonself¡É nucleic acids, and like TLR signaling, a classical ligand-receptor-adaptor model of PRR signaling has been proposed for RLH-mediated signaling, culminating in the induction of antiviral type-1 interferon cytokines, such as IFN-¦Â and IFN-¦Á.

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7.

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7.

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7.

PMID: 18549796 The activation of TBK1 and IKK-? results in the phosphorylation and subsequent dimerization and nuclear translocation of the transcription factors IRF3 and IRF7.

PMID: 18549796 Because it is known that both NF-¦ÊB and IRF3 and IRF7 are required for the assembly of an enhancesome complex required for the induction of IFN-¦Â and IFN-¦Á promoters, the essential role of MAVS in the activation of both of these transcription factors further emphasizes the importance of this mitochondrial adaptor protein in type-1 interferon signaling.

PMID: 18549796 Because it is known that both NF-¦ÊB and IRF3 and IRF7 are required for the assembly of an enhancesome complex required for the induction of IFN-¦Â and IFN-¦Á promoters, the essential role of MAVS in the activation of both of these transcription factors further emphasizes the importance of this mitochondrial adaptor protein in type-1 interferon signaling.

PMID: 18549796, 18272355 The MAVS proline-rich domain contains a TRAF3-binding site required for association with TRAF3 and essential for MAVS-mediated activation of type-1 interferon, but not NF-¦ÊB.

PMID: 18549796 In fact, RIG-I-mediated production of IFN can, in turn, increase the transcription of RIG-I itself, thus setting into motion an IFN amplification loop, which if left unchecked, could become deleterious to the host.

PMID: 18549796, 18262678 similar to RIG-I, LGP2 is inducible by IFN-¦Â, virus, or dsRNA and can bind viral RNA through a RIG-I-like C-terminal domain.

PMID: 18549796, 18262678 similar to RIG-I, LGP2 is inducible by IFN-¦Â, virus, or dsRNA and can bind viral RNA through a RIG-I-like C-terminal domain.

PMID: 18549796 The ligands for RIG-I and MDA-5 are viral ¡Ènonself¡É nucleic acids, and like TLR signaling, a classical ligand-receptor-adaptor model of PRR signaling has been proposed for RLH-mediated signaling, culminating in the induction of antiviral type-1 interferon cytokines, such as IFN-¦Â and IFN-¦Á.

PMID: 18549796, 18262678 similar to RIG-I, LGP2 is inducible by IFN-¦Â, virus, or dsRNA and can bind viral RNA through a RIG-I-like C-terminal domain.

PMID: 18549796 Another intriguing property of LGP2 is its ability to associate with MAVS despite the loss of CARDs.

PMID: 18549796 LGP2 contains a RIG-I-like repression domain (RD) capable of inhibiting RIG-I multimerization and signaling.

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PMID: 18549796, 17460044 The IFN-inducible ubiquitin ligase RNF125 was found to conjugate lysine 48-linked polyubiquitin chains to RIG-I or MDA-5 and cause the proteosomal degradation of either protein.