NF-kappaB activation: Tax sumoylation is out, but what about Tax ubiquitination?

Activation of the NF-κB transcription factors by the viral protein Tax plays a vital role in the pathogenesis of diseases associated with human T-cell lymphotropic virus type I (HTLV-I). The Tax oncoprotein undergoes constitutive K63-linked ubiquitination and sumoylation; however, the roles and molecular mechanisms of these post-translational modifications in Tax-mediated NF-κB activation are being debated. Here, we discuss our current understanding of Tax activation of NF-κB, with a focus on the controversies and the challenges that we are facing.