title: Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK.
abstract: The Tax oncoprotein of human T-cell leukaemia virus type I (HTLV-I) persistently activates nuclear factor-kappaB (NF-kappaB), which is required for HTLV-I-mediated T-cell transformation. Tax activates NF-kappaB by stimulating the activity of IkappaB kinase (IKK), but the underlying mechanism remains elusive. Here, we show that Tax functions as an intracellular stimulator of an IKK-activating kinase, Tak1 (TGF-beta-activating kinase 1). In addition, Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1. In HTLV-I-infected T cells, Tak1 is constitutively activated and complexed with both Tax and IKK. We provide genetic evidence that Tak1 is essential for Tax-induced IKK activation. Furthermore, unlike cellular stimuli, the Tax-specific NF-kappaB signalling does not require the ubiquitin-binding function of IKKgamma. These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells.
authors.affiliation: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, PO Box 850, Hershey, Pennsylvania 17033, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D016356:Gene Products, tax; D016328:NF-kappa B; D051550:I-kappa B Kinase