Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF‐3 and CBP/p300
Mitsutoshi Yoneyama,Wakako Suhara,Yukiko Fukuhara,Makoto Fukuda,Eisuke Nishida,Takashi Fujita +5 more
TLDR
It is demonstrated that IRF‐3 transmits a virus‐induced signal from the cytoplasm to the nucleus, and it is suggested that IRf‐3 plays an important role in the virus‐inducible primary activation of type I IFN and IFN‐responsive genes.Abstract:
It has been hypothesized that certain viral infections directly activate a transcription factor(s) which is responsible for the activation of genes encoding type I interferons (IFNs) and interferon-stimulated genes (ISGs) via interferon regulatory factor (IRF) motifs present in their respective promoters. These events trigger the activation of defense machinery against viruses. Here we demonstrate that IRF-3 transmits a virus-induced signal from the cytoplasm to the nucleus. In unstimulated cells, IRF-3 is present in its inactive form, restricted to the cytoplasm due to a continuous nuclear export mediated by nuclear export signal, and it exhibits few DNA-binding properties. Virus infection but not IFN treatment induces phosphorylation of IRF-3 on specific serine residues, thereby allowing it to complex with the co-activator CBP/p300 with simultaneous nuclear translocation and its specific DNA binding. We also show that a dominant-negative mutant of IRF-3 could inhibit virus-induced activation of chromosomal type I IFN genes and ISGs. These findings suggest that IRF-3 plays an important role in the virus-inducible primary activation of type I IFN and IFN-responsive genes.read more
Citations
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Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
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The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
Mitsutoshi Yoneyama,Mika Kikuchi,Takashi Natsukawa,Noriaki Shinobu,Tadaatsu Imaizumi,Makoto Miyagishi,Kazunari Taira,Shizuo Akira,Takashi Fujita +8 more
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
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Toll-like receptors in innate immunity.
Kiyoshi Takeda,Shizuo Akira +1 more
TL;DR: Toll-like receptors-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders, and the involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed.
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Antiviral Actions of Interferons
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.
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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.
References
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Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Journal ArticleDOI
The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
TL;DR: It is demonstrated that p300/CBP acetylates nucleosomes in concert with PCAF, a novel class of acetyltransferases in that it does not have the conserved motif found among various other acetyl transferases.
Journal ArticleDOI
Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Wei Gu,Robert G. Roeder +1 more
TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
Journal ArticleDOI
CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals
TL;DR: It is concluded that CRM1 is an export receptor for leucine-rich nuclear export signals and a model for the role of RanGTP inCRM1 function and in nuclear export in general is discussed.
Book ChapterDOI
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
TL;DR: This chapter discusses the phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates, a powerful technique to help determine peptide structure and composition of proteins.