Is there a role for ubiquitin or SUMO in human T-cell leukemia virus type 2 Tax-induced NE-κB activation?

Evaluation of: Journo C, Bonnet A, Favre-Bonvin A et al. HTLV-2 Tax-mediated NF-kappa B activation involves a mechanism independent of Tax conjugation to ubiquitin and SUMO. J. ViroL 87(2), 1123-1136 (2012). It is well established that the human T-cell leukemia virus type 1-encoded oncoprotein Tax (Taxi) undergoes polyubiquitination as part of its mechanism to persistently activate NE-kappa B, However, it remains unclear whether Tax2 encoded by the closely related human T-cell leukemia virus type 2 utilizes any post-translational mechanisms to activate NF-kappa B. This study examines the role of ubiquitination and SUMOylation in Tax2 activation of NF-kappa B. The authors have demonstrated that, in contrast to Taxi, Tax2 is not conjugated by ubiquitin or SUMO proteins. Overexpression of the E2 ubiquitin-conjugating enzyme Ubc13 specifically enhances Taxi, but not Tax2, ubiquitination and NE-kappa B activation. Furthermore, a Tax2 lysineless mutant that is unable to be ubiquitinated, SUMOylated or acetylated retains NEMO/IKK gamma interactions and activation of the NE-kappa B pathway. Together, these results provide evidence that Taxi and Tax2 utilize distinct mechanisms to activate NF-kappa B.