Theileria-induced constitutive IKK activation is independent of functional Hsp90 |
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Authors: | Hermann Pascal Dobbelaere Dirk A |
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Affiliation: | Division of Molecular Pathology, Vetsuisse Faculty Bern, L?nggassstrasse 122, CH-3012 Bern, Switzerland. |
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Abstract: | 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. |
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Keywords: | Ab, antibody EMSA, electrophoretic mobility shift assay GA, geldanamycin Hsp90, heat shock protein 90 NEMO, NF-κB essential modulator NF-κB, nuclear factor kappaB IKK, IκBα kinase TNF, tumor necrosis factor |
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