Mechanisms of NF-kappaB activation by the HTLV type 1 tax protein.

The Tax protein encoded by the human T cell leukemia virus type I virus (HTLV-1) activates the expression of both viral genes and cellular genes involved in T lymphocyte growth and proliferation. One of the critical cellular pathways activated by Tax is NF-kappaB. NF-kappaB is normally sequestered in the cytoplasm, bound to a family of inhibitory proteins known as I-kappaB. In contrast to the transient activation of the NF-kappaB pathway seen in response to cytokines, Tax results in constitutive nuclear levels of NF-kappaB. Tax activation of the NF-kappaB pathway is mediated by its ability to enhance the phosphorylation and subsequent degradation of I-kappaB. The persistent activation of the NF-kappaB pathway by Tax is believed to be one of the major events involved in HTLV-1-mediated cellular transformation of T lymphocytes. This review summarizes data exploring the role of Tax in activating the NF-kappaB pathway and discusses our studies to determine the mechanism by which Tax activates the NF-kappaB pathway.