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Roberts, Tara L; Idris, Adi; Dunn, Jasmyn A; Kelly, Greg M; Burnton, Carol M; Hodgson, Samantha; Hardy, Lani L; Garceau, Valerie; Sweet, Matthew J; Ross, Ian L; Hume, David A; Stacey, Katryn J
Science, 02/2009, Volume: 323, Issue: 5917Journal Article
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.
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