Literature DB >> 19158679

An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.

Tilmann Bürckstümmer1, Christoph Baumann, Stephan Blüml, Evelyn Dixit, Gerhard Dürnberger, Hannah Jahn, Melanie Planyavsky, Martin Bilban, Jacques Colinge, Keiryn L Bennett, Giulio Superti-Furga.   

Abstract

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.

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Year:  2009        PMID: 19158679     DOI: 10.1038/ni.1702

Source DB:  PubMed          Journal:  Nat Immunol        ISSN: 1529-2908            Impact factor:   25.606


  28 in total

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6.  Activation of the NLRP3 inflammasome by intracellular poly I:C.

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10.  Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1.

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