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Hijacking of Host Cell IKK Signalosomes by the Transforming Parasite Theileria
Volker T. Heussler,1*Sven Rottenberg,1*Rebekka Schwab,1Peter Küenzi,1Paula C. Fernandez,1Susan McKellar,2Brian Shiels,2Zhijian J. Chen,3Kim Orth,3David Wallach,4Dirk A. E. Dobbelaere1
Parasites have evolved a plethora of mechanisms to
ensure their propagation and evade antagonistic host responses. The
intracellularprotozoan parasite Theileria is the only
eukaryote known to induceuncontrolled host cell proliferation.
Survival of Theileria-transformedleukocytes depends
strictly on constitutive nuclear factor kappaB (NF-B) activity. We
found that this was mediated by recruitmentof the multisubunit IB
kinase (IKK) into large, activated focion the parasite surface. IKK
signalosome assembly was specificfor the transforming schizont stage
of the parasite and was down-regulatedupon differentiation into the
nontransforming merozoite stage.Our findings provide insights into IKK
activation and how pathogenssubvert host-cell signaling
1 Division of Molecular Pathology,
Institute of Animal Pathology, University of Bern, CH-3012 Bern,
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.
Present address: Berhard-Nocht-Institute for Tropical
Medicine, D-20359 Hamburg, Germany.
To whom correspondence should be addressed: E-mail:
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