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HIN-200 Proteins Regulate Caspase Activation in Response to Foreign Cytoplasmic DNA

Research output: Contribution to journalArticle

  • Tara L. Roberts
  • 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

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)1057-1060
Number of pages4
JournalScience
Volume323
Issue number5917
DOIs
StatePublished - 20 Feb 2009

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.

Research areas

  • INNATE IMMUNE-RESPONSE, CELL-DEATH, FAMILY, GENE, MACROPHAGES, RECOGNITION, INFECTION, SIGNALS, DOMAIN, LUPUS

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