It is well established that the human T-cell leukemia virus type 1-encoded oncoprotein Tax (Tax1) undergoes polyubiquitination as part of its mechanism to persistently activate NF-κB. 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-κB. This study examines the role of ubiquitination and SUMOylation in Tax2 activation of NF-κB. The authors have demonstrated that, in contrast to Tax1, Tax2 is not conjugated by ubiquitin or SUMO proteins. Overexpression of the E2 ubiquitin-conjugating enzyme Ubc13 specifically enhances Tax1, but not Tax2, ubiquitination and NF-κB activation. Furthermore, a Tax2 lysineless mutant that is unable to be ubiquitinated, SUMOylated or acetylated retains NEMO/IKKγ interactions and activation of the NF-κB pathway. Together, these results provide evidence that Tax1 and Tax2 utilize distinct mechanisms to activate NF-κB.
Keywords: HTLV-1; HTLV-2; NF-κB; SUMOylation; Tax; ubiquitination.