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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

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

Keywords / Materials (for Non-textual outputs)

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

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