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. 2009 Feb 20;323(5917):1057-60.
doi: 10.1126/science.1169841. Epub 2009 Jan 8.

HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA

Tara L Roberts  1 , Adi Idris, Jasmyn A Dunn, Greg M Kelly, Carol M Burnton, Samantha Hodgson, Lani L Hardy, Valerie Garceau, Matthew J Sweet, Ian L Ross, David A Hume, Katryn J Stacey
Affiliations

HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA

Tara L Roberts et al. Science. .

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. VSports手机版.

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