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.

Subscribe

Logo for

Science 298 (5595): 1033-1036

Copyright © 2002 by the American Association for the Advancement of Science

Hijacking of Host Cell IKK Signalosomes by the Transforming Parasite Theileria

Volker T. Heussler,1*dagger Sven Rottenberg,1* Rebekka Schwab,1 Peter Küenzi,1 Paula C. Fernandez,1 Susan McKellar,2 Brian Shiels,2 Zhijian J. Chen,3 Kim Orth,3 David Wallach,4 Dirk A. E. Dobbelaere1ddagger

Parasites have evolved a plethora of mechanisms to ensure their propagation and evade antagonistic host responses. The intracellular protozoan parasite Theileria is the only eukaryote known to induce uncontrolled host cell proliferation. Survival of Theileria-transformed leukocytes depends strictly on constitutive nuclear factor kappa B (NF-kappa B) activity. We found that this was mediated by recruitment of the multisubunit Ikappa B kinase (IKK) into large, activated foci on the parasite surface. IKK signalosome assembly was specific for the transforming schizont stage of the parasite and was down-regulated upon differentiation into the nontransforming merozoite stage. Our findings provide insights into IKK activation and how pathogens subvert host-cell signaling pathways.

1 Division of Molecular Pathology, Institute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland.
2 Department of Veterinary Parasitology, University of Glasgow, Glasgow G61-1QH Scotland.
3 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
4 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
*   These authors contributed equally to this work.

dagger    Present address: Berhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.

ddagger    To whom correspondence should be addressed: E-mail: dirk.dobbelaere{at}itpa.unibe.ch



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SMYD3 Promotes Cancer Invasion by Epigenetic Upregulation of the Metalloproteinase MMP-9.
A. M. Cock-Rada, S. Medjkane, N. Janski, N. Yousfi, M. Perichon, M. Chaussepied, J. Chluba, G. Langsley, and J. B. Weitzman (2012)
Cancer Res. 72, 810-820
   Abstract »    Full Text »    PDF »
Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata.
N. D. MacHugh, W. Weir, A. Burrells, R. Lizundia, S. P. Graham, E. L. Taracha, B. R. Shiels, G. Langsley, and W. I. Morrison (2011)
Infect. Immun. 79, 2059-2069
   Abstract »    Full Text »    PDF »
Review: Innate immunity to tropical theileriosis.
J. S. Ahmed, E. J. Glass, D. A. Salih, and U. Seitzer (2008)
Innate Immunity 14, 5-12
   Abstract »    PDF »
The Apicomplexan Pathogen Neospora caninum Inhibits Host Cell Apoptosis in the Absence of Discernible NF-{kappa}B Activation.
R. K. Herman, R. E. Molestina, A. P. Sinai, and D. K. Howe (2007)
Infect. Immun. 75, 4255-4262
   Abstract »    Full Text »    PDF »
Type I IFN Induction in Response to Listeria monocytogenes in Human Macrophages: Evidence for a Differential Activation of IFN Regulatory Factor 3 (IRF3).
T. Reimer, M. Schweizer, and T. W. Jungi (2007)
J. Immunol. 179, 1166-1177
   Abstract »    Full Text »    PDF »
c-Jun NH2-Terminal Kinase/c-Jun Signaling Promotes Survival and Metastasis of B Lymphocytes Transformed by Theileria..
R. Lizundia, M. Chaussepied, M. Huerre, D. Werling, J. P. Di Santo, and G. Langsley (2006)
Cancer Res. 66, 6105-6110
   Abstract »    Full Text »    PDF »
Signaling During Pathogen Infection.
S. Munter, M. Way, and F. Frischknecht (2006)
Sci. STKE 2006, re5
   Abstract »    Full Text »    PDF »
Initiation and termination of NF-{kappa}B signaling by the intracellular protozoan parasite Toxoplasma gondii.
S. Shapira, O. S. Harb, J. Margarit, M. Matrajt, J. Han, A. Hoffmann, B. Freedman, M. J. May, D. S. Roos, and C. A. Hunter (2005)
J. Cell Sci. 118, 3501-3508
   Abstract »    Full Text »    PDF »
Survival of protozoan intracellular parasites in host cells.
P. Leiriao, C. D. Rodrigues, S. S. Albuquerque, and M. M. Mota (2004)
EMBO Rep. 5, 1142-1147
   Abstract »    Full Text »    PDF »
Hsp70 promotes TNF-mediated apoptosis by binding IKK{gamma} and impairing NF-{kappa}B survival signaling.
R. Ran, A. Lu, L. Zhang, Y. Tang, H. Zhu, H. Xu, Y. Feng, C. Han, G. Zhou, A. C. Rigby, et al. (2004)
Genes & Dev. 18, 1466-1481
   Abstract »    Full Text »    PDF »
Activation of NF-{kappa}B by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated I{kappa}B to the parasitophorous vacuole membrane.
R. E. Molestina, T. M. Payne, I. Coppens, and A. P. Sinai (2003)
J. Cell Sci. 116, 4359-4371
   Abstract »    Full Text »    PDF »
Theileria parva-Transformed T Cells Show Enhanced Resistance to Fas/Fas Ligand-Induced Apoptosis.
P. Kuenzi, P. Schneider, and D. A. E. Dobbelaere (2003)
J. Immunol. 171, 1224-1231
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882