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EMBO reports 8, 5, 510–515 (2007)
doi:10.1038/sj.embor.7400931
AOP Published online: 16 March 2007
Retroviral oncoprotein Tax deregulates NF- B by activating Tak1 and mediating the physical association of Tak1–IKK
Xuefeng Wu & Shao-Cong Sun
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Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, PO Box 850, Hershey, Pennsylvania 17033, USA
To whom correspondence should be addressed
Shao-Cong Sun Tel: +1 717 531 4164; Fax: +1 717 531 6522; E-mail: sxs70@psu.edu
Received 23 November 2006; Accepted 29 January 2007; Published online 16 March 2007.
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Abstract
The Tax oncoprotein of human T-cell leukaemia virus type I (HTLV-I) persistently activates nuclear factor-B (NF-B), which is required for HTLV-I-mediated T-cell transformation. Tax activates NF-B by stimulating the activity of IB 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- -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-B signalling does not require the ubiquitin-binding function of IKK . These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells.
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