HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA.
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.
Roberts
Tara L
TL
The University of Queensland, Institute for Molecular Bioscience, QLD 4072, Australia.
Idris
Adi
A
Dunn
Jasmyn A
JA
Kelly
Greg M
GM
Burnton
Carol M
CM
Hodgson
Samantha
S
Hardy
Lani L
LL
Garceau
Valerie
V
Sweet
Matthew J
MJ
Ross
Ian L
IL
Hume
David A
DA
Stacey
Katryn J
KJ
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D004789:Enzyme Activation; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D027981:Symporters; D014162:Transfection
D004268:DNA-Binding Proteins; C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C486338:Matp protein, mouse; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition; D027981:Symporters; D004247:DNA; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020170:Caspase 1