Hijacking of host cell IKK signalosomes by the transforming parasite Theileria.
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-kappaB) activity. We found that this was mediated by recruitment of the multisubunit IkappaB 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.
Heussler
Volker T
VT
Division of Molecular Pathology, Institute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland.
Rottenberg
Sven
S
Schwab
Rebekka
R
Küenzi
Peter
P
Fernandez
Paula C
PC
McKellar
Susan
S
Shiels
Brian
B
Chen
Zhijian J
ZJ
Orth
Kim
K
Wallach
David
D
Dobbelaere
Dirk A E
DA
D021581:Active Transport, Cell Nucleus; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D017209:Apoptosis; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology / Q000469:parasitology* / Q000502:physiology; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D016794:Theileria / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*
D000981:Antiprotozoal Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009285:Naphthoquinones; C046326:buparvaquone; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase