Mechanisms of NF-κB Activation by the HTLV Type 1 Tax Protein

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Abstract
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-κB. NF-κB is normally sequestered in the cytoplasm, bound to a family of inhibitory proteins known as I-κB. In contrast to the transient activation of the NF-κB pathway seen in response to cytokines, Tax results in constitutive nuclear levels of NF-κB. Tax activation of the NF-κB pathway is mediated by its ability to enhance the phosphorylation and subsequent degradation of I-κB. The persistent activation of the NF-κB 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-κB pathway and discusses our studies to determine the mechanism by which Tax activates the NF-κB pathway.