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 I kappa B kinase (IKK), resulting in permanently high levels of activated nuclear factor (NF)-kappa B. 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, I kappa B alpha and p65 phosphorylation, NF-kappa B nuclear translocation and DNA binding activity are largely resistant to GA and also NF-kappa B-dependent reporter gene expression is only partly affected. Our findings indicate that parasite-induced IKK activity does not require functional Hsp90. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.