An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome
Copyright policy )An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome
Cytoplasmic DNA triggers activation of the innate immune system. Although 'downstream' signaling components have been characterized, the DNA-sensing components remain elusive. Here we present a systematic proteomics screen for proteins that associate with DNA, 'crossed' to a screen for transcripts induced by interferon-beta, which identified AIM2 as a candidate cytoplasmic DNA sensor. AIM2 showed specificity for double-stranded DNA. It also recruited the inflammasome adaptor ASC and localized to ASC 'speckles'. A decrease in AIM2 expression produced by RNA-mediated interference impaired DNA-induced maturation of interleukin 1beta in THP-1 human monocytic cells, which indicated that endogenous AIM2 is required for DNA recognition. Reconstitution of unresponsive HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1beta showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.
Proteomics, Gene Expression Profiling, Caspase 1, Interleukin-1beta, Nuclear Proteins, DNA, Genomics, Interferon-beta, Immunity, Innate, DNA-Binding Proteins, Mice, Cytosol, NIH 3T3 Cells, Animals, Humans, Adaptor Proteins, Signal Transducing
Proteomics, Gene Expression Profiling, Caspase 1, Interleukin-1beta, Nuclear Proteins, DNA, Genomics, Interferon-beta, Immunity, Innate, DNA-Binding Proteins, Mice, Cytosol, NIH 3T3 Cells, Animals, Humans, Adaptor Proteins, Signal Transducing
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