{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:33:43Z","timestamp":1790004823367,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>Human T\u2010cell leukemia virus type 1 (<jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101) is the etiological agent of adult T cell leukemia (<jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>), which is an aggressive form of T\u2010cell malignancy. <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 oncoproteins, Tax and <jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content>, play crucial roles in the immortalization of T\u2010cells and\/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cells have reduced expression of the <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11B tumor suppressor protein. In the present study, we explored whether Tax and\/or <jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content> play a role in downregulating <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cells. Lentiviral transduction of Tax in a human T\u2010cell line repressed the expression of <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> at both the protein and m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels, whereas the transduction of <jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content> had little effect on the expression. Tax mutants with a decreased activity for the <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CREB<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">PDZ<\/jats:styled-content> protein pathways still showed a reduced expression of the <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> protein, thereby implicating a different function of Tax in <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> downregulation. In addition, the <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20102 Tax2 protein reduced the <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> protein expression in T\u2010cells. Seven <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cell lines, including three <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\u2010derived cell lines, showed reduced <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein expression relative to an uninfected T\u2010cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> protein expression in <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cells; Tax\u2010mediated repression of <jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>11<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> is another mechanism that Tax uses to promote oncogenesis of <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected T\u2010cells.<\/jats:p>","DOI":"10.1111\/cas.12618","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T06:30:58Z","timestamp":1421994658000},"page":"461-465","source":"Crossref","is-referenced-by-count":16,"title":["Human <scp>T<\/scp>\u2010cell leukemia virus type 1 <scp>T<\/scp>ax oncoprotein represses the expression of the <scp>BCL<\/scp>11<scp>B<\/scp> tumor suppressor in <scp>T<\/scp>\u2010cells"],"prefix":"10.1111","volume":"106","author":[{"given":"Takayuki","family":"Takachi","sequence":"first","affiliation":[{"name":"Division of Virology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Division of Pediatrics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Virology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Takahashi\u2010Yoshita","sequence":"additional","affiliation":[{"name":"Division of Virology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Center for Fostering Innovative Leadership Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Division of Virology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Obata","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Mishima","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujiro","family":"Okuda","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Immunology Graduate School and Faculty of Medicine University of the Ryukyus Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Control Institute for Virus Research Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Division of Pediatrics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Green","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research The Ohio State University Columbus OH 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