Abstract
The TIR domain-containing adapter protein TRIP is critically involved in TLR3-induced IFN-beta production through activation of NF-kappaB and ISRE. In addition, TRIF also induces apoptosis when overexpressed in 293 cells. In this report, we demonstrate that PIASy, a member of the PIAS SUMO-ligase family, interacts with TRIP, IRF-3 and IRF-7. In reporter gene assays, PIASy dramatically inhibits TRIF-induced NF-kappaB, ISRE and IFN-beta activation but not TRIF-induced apoptosis. Furthermore, PIASy also inhibits IRF-3, IRF-7 and Sendai virus-induced ISRE activation. Our results suggest that PIASy is an inhibitor of TRIF-induced ISRE and NF-kappaB activation but not apoptosis.
MeSH terms
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Adaptor Proteins, Vesicular Transport / metabolism*
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Apoptosis*
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Blotting, Western
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Line
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Genes, Dominant
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Genes, Reporter
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Humans
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon-beta / metabolism
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Interferons / metabolism*
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Intracellular Signaling Peptides and Proteins*
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Luciferases / metabolism
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Mutation
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NF-kappa B / metabolism*
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Poly-ADP-Ribose Binding Proteins
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Precipitin Tests
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Protein Binding
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Protein Inhibitors of Activated STAT
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Protein Structure, Tertiary
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Receptors, Tumor Necrosis Factor / metabolism
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Response Elements
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Sendai virus / metabolism
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Transcription Factors / metabolism*
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Transfection
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Substances
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Adaptor Proteins, Vesicular Transport
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Carrier Proteins
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DNA-Binding Proteins
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IRF3 protein, human
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IRF7 protein, human
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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PIAS4 protein, human
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Poly-ADP-Ribose Binding Proteins
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Protein Inhibitors of Activated STAT
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Receptors, Tumor Necrosis Factor
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TICAM-1 protein, mouse
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TICAM1 protein, human
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Transcription Factors
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
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Interferon-beta
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Interferons
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Luciferases