{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:33:45Z","timestamp":1791916425969,"version":"4.3.4"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,1,17]]},"abstract":"<jats:p>\n                    Human T cell leukemia virus type I (HTLV-I) causes adult T cell leukemia (ATL) in 2\u20135% of carriers after a long latent period. An HTLV-I encoded protein, Tax, induces proliferation and inhibits apoptosis, resulting in clonal proliferation of infected cells. However,\n                    <jats:italic>tax<\/jats:italic>\n                    gene expression in ATL cells is disrupted by several mechanisms, including genetic changes in the\n                    <jats:italic>tax<\/jats:italic>\n                    gene and DNA methylation\/deletion of the 5\u2032 long terminal repeat (LTR). Because Tax is the major target of cytotoxic T-lymphocytes\n                    <jats:italic>in vivo<\/jats:italic>\n                    , loss of Tax expression should enable ATL cells to escape the host immune system. The 5\u2032 LTR of HTLV-I is frequently hypermethylated or deleted in ATL cells, whereas the 3\u2032 LTR remains unmethylated and intact, suggesting the involvement of the 3\u2032 LTR in leukemogenesis. Here we show that a gene encoded by the minus strand of the HTLV-I proviral genome,\n                    <jats:italic>HTLV-I basic leucine zipper factor<\/jats:italic>\n                    (\n                    <jats:italic>HBZ<\/jats:italic>\n                    ), is transcribed from 3\u2032-LTR in all ATL cells. Suppression of\n                    <jats:italic>HBZ<\/jats:italic>\n                    gene transcription by short interfering RNA inhibits proliferation of ATL cells. In addition,\n                    <jats:italic>HBZ<\/jats:italic>\n                    gene expression promotes proliferation of a human T cell line. Analyses of T cell lines transfected with mutated\n                    <jats:italic>HBZ<\/jats:italic>\n                    genes showed that\n                    <jats:italic>HBZ<\/jats:italic>\n                    promotes T cell proliferation in its RNA form, whereas HBZ protein suppresses Tax-mediated viral transcription through the 5\u2032 LTR. Thus, the single\n                    <jats:italic>HBZ<\/jats:italic>\n                    gene has bimodal functions in two different molecular forms. The growth-promoting activity of\n                    <jats:italic>HBZ<\/jats:italic>\n                    RNA likely plays an important role in oncogenesis by HTLV-I.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0507631103","type":"journal-article","created":{"date-parts":[[2006,1,9]],"date-time":"2006-01-09T20:39:18Z","timestamp":1136839158000},"page":"720-725","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":550,"title":["<i>HTLV-I basic leucine zipper factor<\/i>\n                    gene mRNA supports proliferation of adult T cell leukemia cells"],"prefix":"10.1073","volume":"103","author":[{"given":"Yorifumi","family":"Satou","sequence":"first","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichirou","family":"Yasunaga","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,1,9]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2002.18520.x"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.475"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02983552"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-2-17"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-2-16"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080115"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400009200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202766"},{"key":"e_1_3_2_10_2","first-page":"4862","volume":"57","year":"1997","unstructured":"Etoh, K., Tamiya, S., Yamaguchi, K., Okayama, A., Tsubouchi, H., Ideta, T., Mueller, N., Takatsuki, K. & Matsuoka, M. 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