The multifaceted oncoprotein Tax: subcellular localization, posttranslational modifications, and NF-κB activation.

The human T-cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Constitutive NF-κB activation by the viral oncoprotein Tax plays a crucial role in the induction and maintenance of cellular proliferation, transformation, and inhibition of apoptosis. In an attempt to provide a general view of the molecular mechanisms of constitutive Tax-induced NF-κB activation, we summarize in this review the recent body of literature that supports a major role for Tax posttranslational modifications, chiefly ubiquitination, and SUMOylation, in the NF-κB activity of Tax. These modifications indeed participate in the control of Tax subcellular localization and modulate its protein-protein interaction potential. Tax posttranslational modifications, which highlight the ability of HTLV-I to optimize its limited viral genome size, might represent an attractive target for the design of new therapies for ATL.