Journal
EMBO REPORTS
Volume 8, Issue 5, Pages 510-515Publisher
WILEY
DOI: 10.1038/sj.embor.7400931
Keywords
HTLV-I; Tax; NF-kappa B; Tak1; IKK
Categories
Funding
- NCI NIH HHS [R01 CA68471, R01 CA94922, R01 CA094922, R01 CA068471] Funding Source: Medline
- NIAID NIH HHS [R01 AI057555] Funding Source: Medline
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The Tax oncoprotein of human T-cell leukaemia virus type I (HTLV-I) persistently activates nuclear factor-kappa B (NF-kappa B), which is required for HTLV-I-mediated T-cell transformation. Tax activates NF-kappa B by stimulating the activity of I kappa B 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-kappa B signalling does not require the ubiquitin-binding function of IKK gamma. 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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