Retroviral oncoprotein Tax deregulates NF‐κB by activating Tak1 and mediating the physical association of Tak1–IKK
- 16 March 2007
- journal article
- Published by EMBO in EMBO Reports
- Vol. 8 (5), 510-515
- https://doi.org/10.1038/sj.embor.7400931
Abstract
The Tax oncoprotein of human T‐cell leukaemia virus type I (HTLV‐I) persistently activates nuclear factor‐κB (NF‐κB), which is required for HTLV‐I‐mediated T‐cell transformation. Tax activates NF‐κB by stimulating the activity of IκB 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‐β‐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‐κB signalling does not require the ubiquitin‐binding function of IKKγ. These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells.Keywords
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