Theileria-induced constitutive IKK activation is independent of functional Hsp90.
The intracellular parasite Theileria induces uncontrolled proliferation and host cell transformation. Parasite-induced transformation is accompanied by constitutive activation of IkappaB kinase (IKK), resulting in permanently high levels of activated nuclear factor (NF)-kappaB. IKK activation pathways normally require heat shock protein 90 (Hsp90), a chaperone that regulates the stability and activity of signalling molecules and can be blocked by the benzoquinone ansamycin compound geldanamycin (GA). In Theileria-transformed cells, IkappaBalpha and p65 phosphorylation, NF-kappaB nuclear translocation and DNA binding activity are largely resistant to GA and also NF-kappaB-dependent reporter gene expression is only partly affected. Our findings indicate that parasite-induced IKK activity does not require functional Hsp90.
Hermann
Pascal
P
Division of Molecular Pathology, Vetsuisse Faculty Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.
Dobbelaere
Dirk A
DA
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D010271:Parasites / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016797:Theileria parva / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D051996:Transcription Factor RelA; D004247:DNA; D051550:I-kappa B Kinase; C001277:geldanamycin