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

doi:10.1126/science.1169841

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

Research output: Contribution to journal › Article › peer-review

730 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1057-1060
Number of pages	4
Journal	Science
Volume	323
Issue number	5917
DOIs	https://doi.org/10.1126/science.1169841
Publication status	Published - 2009

Keywords

DNA-binding proteins
cytoplasm
enzyme activation
immunity

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@article{6aff60c9a68b40b383ec78ca6a242490,

title = "HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA",

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.",

keywords = "DNA-binding proteins, cytoplasm, enzyme activation, immunity",

author = "Roberts, {Tara L.} and Adi Idris and Dunn, {Jasmyn A.} and Kelly, {Greg M.} and Burnton, {Carol M.} and Samantha Hodgson and Hardy, {Lani L.} and Valerie Garceau and Sweet, {Matthew J.} and Ross, {Ian L.} and Hume, {David A.} and Stacey, {Katryn J.}",

year = "2009",

doi = "10.1126/science.1169841",

language = "English",

volume = "323",

pages = "1057--1060",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5917",

}

TY - JOUR

T1 - HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA

AU - Roberts, Tara L.

AU - Idris, Adi

AU - Dunn, Jasmyn A.

AU - Kelly, Greg M.

AU - Burnton, Carol M.

AU - Hodgson, Samantha

AU - Hardy, Lani L.

AU - Garceau, Valerie

AU - Sweet, Matthew J.

AU - Ross, Ian L.

AU - Hume, David A.

AU - Stacey, Katryn J.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - DNA-binding proteins

KW - cytoplasm

KW - enzyme activation

KW - immunity

UR - http://handle.uws.edu.au:8081/1959.7/uws:30331

U2 - 10.1126/science.1169841

DO - 10.1126/science.1169841

M3 - Article

SN - 0036-8075

VL - 323

SP - 1057

EP - 1060

JO - Science

JF - Science

IS - 5917

ER -

HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA

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Keywords

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