A20 is a negative regulator of IFN regulatory factor 3 signaling.
Tatsuya Saitoh,Masahiro Yamamoto,Makoto Miyagishi,Makoto Miyagishi,Kazunari Taira,Kazunari Taira,Makoto Nakanishi,Takashi Fujita,Shizuo Akira,Naoki Yamamoto,Shoji Yamaoka +10 more
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TLDR
This study demonstrates that A20 is a candidate negative regulator of the signaling cascade to IRF-3 activation in the innate antiviral response, and knocking down of A20 expression by RNA interference results in enhanced IRf-3-dependent transcription triggered by the stimulation of TLR3 or virus infection.Abstract:
IFN regulatory factor 3 (IRF-3) is a critical transcription factor that regulates an establishment of innate immune status following detection of viral pathogens. Recent studies have revealed that two IkappaB kinase (IKK)-like kinases, NF-kappaB-activating kinase/Traf family member-associated NF-kappaB activator-binding kinase 1 and IKK-i/IKKepsilon, are responsible for activation of IRF-3, but the regulatory mechanism of the IRF-3 signaling pathway has not been fully understood. In this study, we report that IRF-3 activation is suppressed by A20, which was initially identified as an inhibitor of apoptosis and inducibly expressed by dsRNA. A20 physically interacts with NF-kappaB-activating kinase/Traf family member-associated NF-kappaB activator-binding kinase 1 and IKK-i/IKKepsilon, and inhibits dimerization of IRF-3 following engagement of TLR3 by dsRNA or Newcastle disease virus infection, leading to suppression of the IFN stimulation response element- and IFN-beta promoter-dependent transcription. Importantly, knocking down of A20 expression by RNA interference results in enhanced IRF-3-dependent transcription triggered by the stimulation of TLR3 or virus infection. Our study thus demonstrates that A20 is a candidate negative regulator of the signaling cascade to IRF-3 activation in the innate antiviral response.read more
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Toll-like Receptor and RIG-1-like Receptor Signaling
Taro Kawai,Shizuo Akira +1 more
TL;DR: Recent insights into the signaling pathways initiated by TLR and RLR are reviewed and their roles in innate and adaptive immune responses are reviewed.
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RNA recognition and signal transduction by RIG-I-like receptors.
TL;DR: This review focuses on the current understanding of the molecular machinery underlying RNA recognition and subsequent signal transduction by RLRs.
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The Yin and Yang of type I interferon activity in bacterial infection
TL;DR: An increasing body of work shows that type I IFNs have an important role in the host response to bacterial infection, and can influence various immune effector mechanisms.
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A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-κB activation
Mizuho Hasegawa,Yukari Fujimoto,Peter C. Lucas,Hiroyasu Nakano,Koichi Fukase,Gabriel Núñez,Naohiro Inohara,Naohiro Inohara +7 more
TL;DR: RICK polyubiquitination links TAK1 to IKK complexes, a critical step in Nod1/Nod2‐mediated NF‐κB activation, and is shown to be essential for RICK‐mediated IKK activation and cytokine/chemokine secretion.
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The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology
TL;DR: The intracellular ubiquitin-editing protein A20 is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli and regulates tumor necrosis factor (TNF)-induced apoptosis.
References
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Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
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IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
Katherine A. Fitzgerald,Sarah M. McWhirter,Kerrie L. Faia,Daniel C. Rowe,Eicke Latz,Douglas T. Golenbock,Anthony J. Coyle,Sha-Mei Liao,Tom Maniatis +8 more
TL;DR: It is reported that the noncanonical IκB kinase homologs, IKKε (IKKε) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-κB activation, are also essential components of the IRF3 signaling pathway.
Journal ArticleDOI
Tlr signaling pathways
Kiyoshi Takeda,Shizuo Akira +1 more
TL;DR: Toll-like receptors have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components and TIR domain-containing adaptors provide specificity of TLR signaling.
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Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Sonia Sharma,Benjamin R. tenOever,Nathalie Grandvaux,Guo-Ping Zhou,Rongtuan Lin,John Hiscott +5 more
TL;DR: It is reported here that the IκB kinase (IKK)–related kinases IKKϵ and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRf-3 and IRF-7.