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The <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 proviral integrations. Tax is a potent activator of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB, a key signaling pathway that is essential for the survival and proliferation of <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T cells. However, constitutive <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB\u2010induced senescence can selectively undergo clonal expansion after <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 infection. Tax expression is often silenced in the majority of <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content> due to genetic alterations in the <jats:italic>tax<\/jats:italic> gene or <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> hypermethylation of the 5\u2032\u2010<jats:styled-content style=\"fixed-case\">LTR<\/jats:styled-content>. Despite the loss of Tax, <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation remains persistently activated in <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content> due to somatic mutations in genes in the T\/B\u2010cell receptor (T\/<jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB signaling pathways. In this review, we focus on the key events driving Tax\u2010dependent and \u2010independent mechanisms of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation during the multistep process leading to <jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/febs.14492","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T12:57:18Z","timestamp":1525352238000},"page":"3324-3336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["<scp>NF<\/scp>\u2010\u03baB signaling mechanisms in <scp>HTLV<\/scp>\u20101\u2010induced adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1111","volume":"285","author":[{"given":"Edward William","family":"Harhaj","sequence":"first","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine Baltimore MD 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