Abstract
Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity. We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease (SENP) 2 as a negative regulator of virus-triggered IFN-β induction. Overexpression of SENP2 caused IRF3 deSUMOylation, K48-linked ubiquitination, and degradation, whereas depletion of SENP2 had opposite effects. Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87, and these processes are competitive. The level of virus-triggered IFN-β was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls. Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation, and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism*
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Endopeptidases / genetics
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Endopeptidases / metabolism
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HEK293 Cells
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Humans
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Immunity, Innate / immunology*
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / metabolism*
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Interferon-beta / metabolism
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Mice
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Mice, Knockout
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism*
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RNA Interference
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Sendai virus / immunology*
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Signal Transduction / immunology
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Small Ubiquitin-Related Modifier Proteins / metabolism*
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Sumoylation
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Ubiquitination
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Virus Replication
Substances
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IRF3 protein, human
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Interferon Regulatory Factor-3
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Irf3 protein, mouse
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Multienzyme Complexes
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Small Ubiquitin-Related Modifier Proteins
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Interferon-beta
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Endopeptidases
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SENP1 protein, human
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Cysteine Endopeptidases
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SENP2 protein, human
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Senp1 protein, mouse
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Senp2 protein, mouse