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Science 1 November 2002:
Vol. 298. no. 5595, pp. 1033 - 1036
DOI: 10.1126/science.1075462
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Reports

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

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