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.
Li
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Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Gaynor
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D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D016356:Gene Products, tax / Q000502:physiology*; D015490:HTLV-I Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology*
D016356:Gene Products, tax; D016328:NF-kappa B