Mechanisms of NF-kappa B activation by the HTLV type 1 tax protein

The Tax protein encoded by the human T cell leukemia virus type I virus (HT LV-1) activates the expression of both viral genes and cellular genes invol ved in T lymphocyte growth and proliferation. One of the critical cellular pathways activated by Tax is NF-kappaB. NF-kappaB is normally sequestered i n 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-kap paB. Tax activation of the NF-kappaB pathway is mediated by its ability to enhance the phosphorylation and subsequent degradation of I-kappaB. The per sistent 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 activ ating the NF-kappaB pathway and discusses our studies to determine the mech anism by which Tax activates the NF-kappaB pathway.