Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 8 January 2009
Science 20 February 2009:
Vol. 323. no. 5917, pp. 1057 - 1060
DOI: 10.1126/science.1169841
Prev | Table of Contents | Next

Reports

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

Tara L. Roberts,1,2* Adi Idris,1* Jasmyn A. Dunn,1 Greg M. Kelly,1 Carol M. Burnton,1 Samantha Hodgson,1 Lani L. Hardy,1 Valerie Garceau,1{dagger} Matthew J. Sweet,1,3 Ian L. Ross,1 David A. Hume,1{dagger} Katryn J. Stacey1,3{ddagger}

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.

1 The University of Queensland, Institute for Molecular Bioscience, QLD 4072, Australia.
2 Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia.
3 The University of Queensland, School of Chemistry and Biomolecular Science, QLD 4072, Australia.

* These authors contributed equally to this work.

{dagger} Present address: The Roslin Institute, University of Edinburgh, Roslin EH259PS, Scotland, UK.

{ddagger} To whom correspondence should be addressed. E-mail: k.stacey{at}imb.uq.edu.au

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Female and Male Sex Hormones Differentially Regulate Expression of Ifi202, an Interferon-Inducible Lupus Susceptibility Gene within the Nba2 Interval.
R. Panchanathan, H. Shen, M. G. Bupp, K. A. Gould, and D. Choubey (2009)
J. Immunol. 183, 7031-7038
   Abstract »    Full Text »    PDF »
Interferons Direct an Effective Innate Response to Legionella pneumophila Infection.
C. R. Plumlee, C. Lee, A. A. Beg, T. Decker, H. A. Shuman, and C. Schindler (2009)
J. Biol. Chem. 284, 30058-30066
   Abstract »    Full Text »    PDF »
Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity.
Y. J. Crow and J. Rehwinkel (2009)
Hum. Mol. Genet. 18, R130-R136
   Abstract »    Full Text »    PDF »
Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR.
I Kimkong, Y Avihingsanon, and N Hirankarn (2009)
Lupus 18, 1066-1072
   Abstract »    PDF »
Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation.
R. Kenworthy, D. Lambert, F. Yang, N. Wang, Z. Chen, H. Zhu, F. Zhu, C. Liu, K. Li, and H. Tang (2009)
Nucleic Acids Res. 37, 6587-6599
   Abstract »    Full Text »    PDF »
Requirement for DNA CpG Content in TLR9-Dependent Dendritic Cell Activation Induced by DNA-Containing Immune Complexes.
K. Yasuda, C. Richez, M. B. Uccellini, R. J. Richards, R. G. Bonegio, S. Akira, M. Monestier, R. B. Corley, G. A. Viglianti, A. Marshak-Rothstein, et al. (2009)
J. Immunol. 183, 3109-3117
   Abstract »    Full Text »    PDF »
Vicious circle: systemic autoreactivity in Ro52/TRIM21-deficient mice.
S. Bolland and A. Garcia-Sastre (2009)
J. Exp. Med. 206, 1647-1651
   Abstract »    Full Text »    PDF »
Caspase-8 for Outer Harmony.
G. Sollberger and H.-D. Beer (2009)
Science Signaling 2, pe40
   Abstract »    Full Text »    PDF »
AIMing 2 Detect Foreign DNA.
A. M. Krieg (2009)
Science Signaling 2, pe39
   Abstract »    Full Text »    PDF »
Pyrin Critical to Macrophage IL-1{beta} Response to Francisella Challenge.
M. A. Gavrilin, S. Mitra, S. Seshadri, J. Nateri, F. Berhe, M. W. Hall, and M. D. Wewers (2009)
J. Immunol. 182, 7982-7989
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)