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The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution
by
Fan, Yu-Kuan
, Lin, Jhih-Pu
, Liu, Helene Minyi
in
14-3-3 protein
/ 14-3-3 Proteins - immunology
/ 14-3-3 Proteins - metabolism
/ Activation
/ Antiviral drugs
/ Biochemistry
/ Biology and Life Sciences
/ Cell cycle
/ Cell Line, Tumor
/ Cytoplasm
/ Cytosol
/ DEAD-box RNA Helicases
/ Dengue fever
/ Double-stranded RNA
/ Gene expression
/ Gene Knockdown Techniques
/ HEK293 Cells
/ Humans
/ Immune response
/ Immunity
/ Immunity, Innate
/ Immunostimulation
/ Infections
/ Innate immunity
/ Interferon
/ Interferon-beta - genetics
/ Interferon-beta - immunology
/ Interferon-beta - metabolism
/ Interferon-Induced Helicase, IFIH1 - genetics
/ Interferon-Induced Helicase, IFIH1 - immunology
/ Interferon-Induced Helicase, IFIH1 - metabolism
/ Isoforms
/ Kinases
/ Kinetics
/ Ligands
/ Localization
/ Medicine
/ Medicine and Health Sciences
/ Mitochondria
/ Molecular biology
/ Molecular Chaperones - immunology
/ Molecular Chaperones - metabolism
/ Molecular modelling
/ Oligomerization
/ Peptides
/ Phosphorylation
/ Protein Isoforms
/ Protein Transport
/ Proteins
/ Research and Analysis Methods
/ RNA, Double-Stranded
/ RNA, Messenger - biosynthesis
/ RNA, Messenger - genetics
/ Signal Transduction
/ Viral infections
/ Virus Diseases - immunology
/ Virus Diseases - metabolism
/ Viruses
/ β-Interferon
2019
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The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution
by
Fan, Yu-Kuan
, Lin, Jhih-Pu
, Liu, Helene Minyi
in
14-3-3 protein
/ 14-3-3 Proteins - immunology
/ 14-3-3 Proteins - metabolism
/ Activation
/ Antiviral drugs
/ Biochemistry
/ Biology and Life Sciences
/ Cell cycle
/ Cell Line, Tumor
/ Cytoplasm
/ Cytosol
/ DEAD-box RNA Helicases
/ Dengue fever
/ Double-stranded RNA
/ Gene expression
/ Gene Knockdown Techniques
/ HEK293 Cells
/ Humans
/ Immune response
/ Immunity
/ Immunity, Innate
/ Immunostimulation
/ Infections
/ Innate immunity
/ Interferon
/ Interferon-beta - genetics
/ Interferon-beta - immunology
/ Interferon-beta - metabolism
/ Interferon-Induced Helicase, IFIH1 - genetics
/ Interferon-Induced Helicase, IFIH1 - immunology
/ Interferon-Induced Helicase, IFIH1 - metabolism
/ Isoforms
/ Kinases
/ Kinetics
/ Ligands
/ Localization
/ Medicine
/ Medicine and Health Sciences
/ Mitochondria
/ Molecular biology
/ Molecular Chaperones - immunology
/ Molecular Chaperones - metabolism
/ Molecular modelling
/ Oligomerization
/ Peptides
/ Phosphorylation
/ Protein Isoforms
/ Protein Transport
/ Proteins
/ Research and Analysis Methods
/ RNA, Double-Stranded
/ RNA, Messenger - biosynthesis
/ RNA, Messenger - genetics
/ Signal Transduction
/ Viral infections
/ Virus Diseases - immunology
/ Virus Diseases - metabolism
/ Viruses
/ β-Interferon
2019
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The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution
by
Fan, Yu-Kuan
, Lin, Jhih-Pu
, Liu, Helene Minyi
in
14-3-3 protein
/ 14-3-3 Proteins - immunology
/ 14-3-3 Proteins - metabolism
/ Activation
/ Antiviral drugs
/ Biochemistry
/ Biology and Life Sciences
/ Cell cycle
/ Cell Line, Tumor
/ Cytoplasm
/ Cytosol
/ DEAD-box RNA Helicases
/ Dengue fever
/ Double-stranded RNA
/ Gene expression
/ Gene Knockdown Techniques
/ HEK293 Cells
/ Humans
/ Immune response
/ Immunity
/ Immunity, Innate
/ Immunostimulation
/ Infections
/ Innate immunity
/ Interferon
/ Interferon-beta - genetics
/ Interferon-beta - immunology
/ Interferon-beta - metabolism
/ Interferon-Induced Helicase, IFIH1 - genetics
/ Interferon-Induced Helicase, IFIH1 - immunology
/ Interferon-Induced Helicase, IFIH1 - metabolism
/ Isoforms
/ Kinases
/ Kinetics
/ Ligands
/ Localization
/ Medicine
/ Medicine and Health Sciences
/ Mitochondria
/ Molecular biology
/ Molecular Chaperones - immunology
/ Molecular Chaperones - metabolism
/ Molecular modelling
/ Oligomerization
/ Peptides
/ Phosphorylation
/ Protein Isoforms
/ Protein Transport
/ Proteins
/ Research and Analysis Methods
/ RNA, Double-Stranded
/ RNA, Messenger - biosynthesis
/ RNA, Messenger - genetics
/ Signal Transduction
/ Viral infections
/ Virus Diseases - immunology
/ Virus Diseases - metabolism
/ Viruses
/ β-Interferon
2019
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The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution
Journal Article
The 14-3-3η chaperone protein promotes antiviral innate immunity via facilitating MDA5 oligomerization and intracellular redistribution
2019
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Overview
MDA5 belongs to the RIG-I-like receptor family and plays a non-redundant role in recognizing cytoplasmic viral RNA to induce the production of type I IFNs. Upon RNA ligand stimulation, we observed the redistribution of MDA5 from the cytosol to mitochondrial membrane fractions. However, the molecular mechanisms of MDA5 activation remain less understood. Here we show that 14-3-3η is an essential accessory protein for MDA5-dependent type I IFN induction. We found that several 14-3-3 isoforms may interact with MDA5 through the CARDs (N-MDA5), but 14-3-3η was the only isoform that could enhance MDA5-dependent IFNβ promoter activities in a dose-dependent manner. Knock-down of 14-3-3η in Huh7 cells impaired and delayed the kinetics of MDA5 oligomerization, which is a critical step for MDA5 activation. Consequently, the MDA5-dependent IFNβ promoter activities as well as IFNβ mRNA expression level were also decreased in the 14-3-3η knocked-down cells. We also demonstrated that 14-3-3η is essential in boosting the activation of MDA5-dependent antiviral innate immunity during viral infections. In conclusion, our results uncover a novel function of 14-3-3η to promote the MDA5-dependent IFNβ induction pathway by reducing the immunostimulatory potential of viral dsRNA within MDA5 activation signaling pathway.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ 14-3-3 Proteins - immunology
/ 14-3-3 Proteins - metabolism
/ Cytosol
/ Humans
/ Immunity
/ Interferon-beta - immunology
/ Interferon-beta - metabolism
/ Interferon-Induced Helicase, IFIH1 - genetics
/ Interferon-Induced Helicase, IFIH1 - immunology
/ Interferon-Induced Helicase, IFIH1 - metabolism
/ Isoforms
/ Kinases
/ Kinetics
/ Ligands
/ Medicine
/ Medicine and Health Sciences
/ Molecular Chaperones - immunology
/ Molecular Chaperones - metabolism
/ Peptides
/ Proteins
/ Research and Analysis Methods
/ RNA, Messenger - biosynthesis
/ Viruses
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