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First published online December 9, 2005
doi: 10.1242/10.1242/jcs.02709
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Research Article |
B activation and target gene expression following Toxoplasma gondii infection
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA
* Author for correspondence (e-mail: sinai{at}uky.edu)
Accepted 22 September 2005
Activation of NF-
B by the intracellular pathogen Toxoplasma gondii is associated with the localization of phosphorylated I
B
to the parasitophorous vacuole membrane (PVM). This is mediated by a parasite-derived I
B kinase (TgIKK) activity and is independent of host IKK function. In the present study, we examined the roles of host IKK and parasite-derived TgIKK on the temporal modulation of NF-
B activation. Despite the presence of TgIKK activity at the PVM, nuclear translocation of NF-
B and subsequent gene expression exhibited a requirement for the host IKK complex. A detailed kinetic analysis of NF-
B activation revealed a biphasic, hierarchical and temporally regulated response. We propose a novel paradigm for the modulation of NF-
B-dependent gene expression by T. gondii that involves both the host IKK complex and TgIKK activity at different phases of infection. Thus, T. gondii effectively alters gene expression in a temporal dimension by exploiting the NF-
B signaling machinery and subsequently rewiring the activation circuits of the infected host cell.
Key words: Toxoplasma gondii, IKK, I
B, NF-
B
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