Abstract
The mammalian innate immune system is activated by foreign nucleic acids. Detection of double-stranded DNA (dsDNA) in the cytoplasm triggers characteristic antiviral responses and macrophage cell death. Cytoplasmic dsDNA rapidly activated caspase 3 and caspase 1 in bone marrow-derived macrophages. We identified the HIN-200 family member and candidate lupus susceptibility factor, p202, as a dsDNA binding protein that bound stably and rapidly to transfected DNA. Knockdown studies showed p202 to be an inhibitor of DNA-induced caspase activation. Conversely, the related pyrin domain-containing HIN-200 factor, AIM2 (p210), was required for caspase activation by cytoplasmic dsDNA. This work indicates that HIN-200 proteins can act as pattern recognition receptors mediating responses to cytoplasmic dsDNA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caspase 1 / metabolism*
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Caspase 3 / metabolism*
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Cell Line
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Cytoplasm / metabolism*
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DNA / immunology
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DNA / metabolism*
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DNA-Binding Proteins / isolation & purification
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Immunity, Innate
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / isolation & purification
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Intracellular Signaling Peptides and Proteins / metabolism*
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Macrophages / immunology
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Macrophages / metabolism*
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred Strains
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RNA, Small Interfering
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Receptors, Pattern Recognition / metabolism*
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Symporters
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Transfection
Substances
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DNA-Binding Proteins
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Ifi202b protein, mouse
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Intracellular Signaling Peptides and Proteins
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Matp protein, mouse
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Membrane Proteins
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RNA, Small Interfering
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Receptors, Pattern Recognition
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Symporters
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DNA
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Casp3 protein, mouse
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Caspase 3
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Caspase 1