Tax Ubiquitylation and Sumoylation Control the Two Distinct Steps of NF-κB Activation.

Activation of the NF-κB pathway by the HTLV-I oncoprotein Tax plays a mandatory role in the proliferation and transformation of infected T cells. We have previously demonstrated that Tax is ubiquitylated, mostly on lysine residues located in its carboxy-terminal half. In this study, we investigated the contribution of Tax ubiquitylation on its ability to transactivate the NF-κB pathway. We show that the integrity of C-terminal lysines, and Tax ubiquitylation, are critical for Tax binding to IKK, IKK activation and nuclear translocation of NF-κB. We also report that Tax is post-translationally modified by SUMO on lysine residues also targeted by ubiquitin and that Tax sumoylation occurs in the nucleus and is required for the terminal steps of NF-κB activation. Conversely, Tax ubiquitylation and sumoylation are not involved in CREB activation. Thus, the differential ubiquitylation or sumoylation of the same lysines in Tax regulates essential events controlling the NF-κB pathway, revealing how distinct cellular modifications enrich the functions of this versatile oncoprotein.