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TLR3 recognizes double-stranded (ds)RNA and triggers a signaling pathway via a TIR domain-containing adapter inducing IFN-beta (TRIF) (also known as TICAM-1)</csml:comment>
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TLR3 recognizes double-stranded (ds)RNA and triggers a signaling pathway via a TIR domain-containing adapter inducing IFN-beta (TRIF) (also known as TICAM-1)</csml:comment>
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TRIF associates with TRAF3 and TRAF6 via TRAF-binding motifs which exist in its N-terminal portion and also with receptor interacting protein (RIP) 1 and RIP3 via RIP homotypic interaction motif (RHIM)</csml:comment>
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<csml:comment type="text">PMID: 18694646
Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i).</csml:comment>
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<csml:comment type="text">PMID: 18694646
Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i).</csml:comment>
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<csml:comment type="text">PMID: 18694646
Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i).

PMID: 18694646
Figure 2
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<csml:comment type="text">PMID: 18694646
Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i).

PMID: 18694646
Following the formation of this signaling complex, IRF7 and nuclear factor-kappa B (NF-κB) are activated, which results in the production of type I IFNs and cytokines

PMID: 18694646
Figure 2
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Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i)

PMID: 18694646
Figure 2.</csml:comment>
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TRIF associates with TRAF3, TRAF6 and RIP1. TRAF6 and RIP1 activate NF-KappaB and AP-1 while TRAF3 activates TBK1/IKK-i and is followed by a type I IFN response.</csml:comment>
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TRIF associates with TRAF3, TRAF6 and RIP1. TRAF6 and RIP1 activate NF-KappaB and AP-1 while TRAF3 activates TBK1/IKK-i and is followed by a type I IFN response.</csml:comment>
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TRIF associates with TRAF3, TRAF6 and RIP1. TRAF6 and RIP1 activate NF-KappaB and AP-1 while TRAF3 activates TBK1/IKK-i and is followed by a type I IFN response.</csml:comment>
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<csml:comment type="text">PMID: 18694646
Figure 1 

PMID: 18694646
TRAF6 and RIP1 activate NF-KappaB while TRAF3 activates TRAF family member-associated NK-KappaB activator (TANK)-binding kinase 1 (TBK1) and inducible IKappaB kinase (IKK-i).</csml:comment>
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Tyrosine phosphorylation of TLR3 induces PI3K recruitment to the receptor and subsequent activation of Akt leads to activation of IRF-3.</csml:comment>
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Tyrosine phosphorylation of TLR3 induces PI3K recruitment to the receptor and subsequent activation of Akt leads to activation of IRF-3.</csml:comment>
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Tyrosine phosphorylation of TLR3 induces PI3K recruitment to the receptor and subsequent activation of Akt leads to activation of IRF-3.</csml:comment>
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RIG-I binds 5prime-triphosphorylated single-stranded (ss)RNA and short dsRNA and stimulates production of type I IFNs </csml:comment>
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RIG-I binds 5prime-triphosphorylated single-stranded (ss)RNA and short dsRNA and stimulates production of type I IFNs </csml:comment>
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By contrast, MDA5 preferentially recognizes longer-dsRNA, including synthetic poly-IC</csml:comment>
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By contrast, MDA5 preferentially recognizes longer-dsRNA, including synthetic poly-IC</csml:comment>
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<csml:comment type="text">PMID: 18694646,16127453,16125763,16177806,16153868
Both RIG-I and MDA5 associate with an adapter protein IPS-1 also known as MAVS, VISA or CARDIF, which also contains an N-terminal CARD</csml:comment>
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<csml:comment type="text">PMID: 18694646,16127453,16125763,16177806,16153868
Both RIG-I and MDA5 associate with an adapter protein IPS-1 also known as MAVS, VISA or CARDIF, which also contains an N-terminal CARD</csml:comment>
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<csml:comment type="text"></csml:comment>
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<csml:comment type="text">PMID: 18694646
IPS-1 then associates with TRAF3, followed by activation of TBK1 and Ikk-i. </csml:comment>
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<csml:comment type="text">PMID: 18694646
IPS-1 then associates with TRAF3, followed by activation of TBK1 and Ikk-i. </csml:comment>
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<csml:comment type="text">PMID: 18694646
IPS-1 then associates with TRAF3, followed by activation of TBK1 and Ikk-i. </csml:comment>
</csml:comments>
</csml:process>
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IPS-1 then associates with TRAF3, followed by activation of TBK1 and Ikk-i. </csml:comment>
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These kinases phosphorylate IRF3 and IRF7 and induce type I IFN production </csml:comment>
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These kinases phosphorylate IRF3 and IRF7 and induce type I IFN production </csml:comment>
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These kinases phosphorylate IRF3 and IRF7 and induce type I IFN production </csml:comment>
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These kinases phosphorylate IRF3 and IRF7 and induce type I IFN production </csml:comment>
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Figure 1</csml:comment>
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TLR7 signals through a TIR domain-containing adapter, myeloid differentiation factor 88 (MyD88).</csml:comment>
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Upon exposure to its ligand, MyD88 forms a complex with interleukin-1-receptor (IL-1R)-associated kinase-4 (IRAK-4), IRAK-1, tumor necrosis factor-receptor associated factor 3 (TRAF3), TRAF6, Ikkalpha and IRF-7</csml:comment>
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Following the formation of this signaling complex, IRF7 and nuclear factor-kappa B (NF-κB) are activated, which results in the production of type I IFNs and cytokines

PMID: 18694646
Figure 2</csml:comment>
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Following the formation of this signaling complex, IRF7 and nuclear factor-kappa B (NF-κB) are activated, which results in the production of type I IFNs and cytokines</csml:comment>
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Figure 1</csml:comment>
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Following the formation of this signaling complex, IRF7 and nuclear factor-kappa B (NF-κB) are activated, which results in the production of type I IFNs and cytokines</csml:comment>
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TLR9 recognizes unmethylated DNA with a CpG motif (CpG-DNA) and DNA viruses, including herpes simplex virus (HSV)-1, HSV-2 and cytomegalovirus (CMV) in pDCs.</csml:comment>
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TLR9 shares the adapter protein MyD88 and the downstream signaling pathway with TLR7.</csml:comment>
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Upon exposure to its ligand, MyD88 forms a complex with interleukin-1-receptor (IL-1R)-associated kinase-4 (IRAK-4), IRAK-1, tumor necrosis factor-receptor associated factor 3 (TRAF3), TRAF6, Ikkalpha and IRF-7</csml:comment>
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Figure2</csml:comment>
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cDCs and macrophages also respond to CpG-DNA and produce small amounts of IFN-beta through IRF-1 activation rather than IRF-3 or IRF-7 activation</csml:comment>
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cDCs and macrophages also respond to CpG-DNA and produce small amounts of IFN-beta through IRF-1 activation rather than IRF-3 or IRF-7 activation</csml:comment>
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Recently endoplasmic reticulum (ER) protein UNC93B1 turned out to be essential for trafficking of TLR7 and TLR9 from ER to endosome,but what triggers this TLR-trafficking from ER to endosome before viral recognition by TLRs remains to be elucidated. </csml:comment>
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Recently endoplasmic reticulum (ER) protein UNC93B1 turned out to be essential for trafficking of TLR7 and TLR9 from ER to endosome,but what triggers this TLR-trafficking from ER to endosome before viral recognition by TLRs remains to be elucidated. </csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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IPS-1 also interacts with Fas-associated death domain-containing protein (FADD) and leads to activation of NF-KappaB through cleavage of caspase-8/-10</csml:comment>
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