HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA
Science, 2009•science.org
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 …
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 …
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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