{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:54:33Z","timestamp":1791312873338,"version":"4.3.1"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T00:00:00Z","timestamp":1300147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia\/lymphoma (ATL), a malignancy of CD4\n            <jats:sup>+<\/jats:sup>\n            T cells whose etiology is thought to be associated with the viral\n            <jats:italic>trans<\/jats:italic>\n            -activator Tax. We have shown recently that Tax can drastically upregulate the expression of p27\n            <jats:sup>Kip1<\/jats:sup>\n            and p21\n            <jats:sup>CIP1\/WAF1<\/jats:sup>\n            through protein stabilization and mRNA\n            <jats:italic>trans<\/jats:italic>\n            -activation and stabilization, respectively. The Tax-induced surge in p21\n            <jats:sup>CIP1\/WAF1<\/jats:sup>\n            and p27\n            <jats:sup>Kip1<\/jats:sup>\n            begins in S phase and results in cellular senescence. Importantly, HeLa and SupT1 T cells infected by HTLV-1 also arrest in senescence, thus challenging the notion that HTLV-1 infection causes cell proliferation. Here we use time-lapse microscopy to investigate the effect of Tax on cell cycle progression in two reporter cell lines, HeLa\/18x21-EGFP and HeLa-FUCCI, that express enhanced green fluorescent protein (EGFP) under the control of 18 copies of the Tax-responsive 21-bp repeat element and\n            <jats:underline>f<\/jats:underline>\n            luorescent\n            <jats:underline>u<\/jats:underline>\n            biquitin\n            <jats:underline>c<\/jats:underline>\n            ell\n            <jats:underline>c<\/jats:underline>\n            ycle\n            <jats:underline>i<\/jats:underline>\n            ndicators, respectively. Tax-expressing HeLa cells exhibit elongated or stalled cell cycle phases. Many of them bypass mitosis and become single senescent cells as evidenced by the expression of senescence-associated \u03b2-galactosidase. Such cells have twice the normal equivalent of cellular contents and hence are enlarged, with exaggerated nuclei. Interestingly, nocodazole treatment revealed a small variant population of HeLa\/18x21-EGFP cells that could progress into mitosis normally with high levels of Tax expression, suggesting that genetic or epigenetic changes that prevent Tax-induced senescence can occur spontaneously at a detectable frequency.\n          <\/jats:p>","DOI":"10.1128\/jvi.00086-10","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T03:02:26Z","timestamp":1294282946000},"page":"3001-3009","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Complex Cell Cycle Abnormalities Caused by Human T-Lymphotropic Virus Type 1 Tax"],"prefix":"10.1128","volume":"85","author":[{"given":"Liangpeng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoe","family":"Kotomura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yik-Khuan","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bixler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Schell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chou-Zen","family":"Giam","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1645","volume":"12","year":"1996","unstructured":"Akagi, T., H. Ono, and K. Shimotohno. 1996. Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1\/Cip1\/Sdi1. Oncogene 12:1645-1652.","journal-title":"Oncogene"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.11.023"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02331-07"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11316"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804931200"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2741\/2163"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.379706"},{"key":"e_1_3_3_9_2","first-page":"2468","volume":"47","year":"1987","unstructured":"Graziano, S. L., et al. 1987. Quantitative assay of human T-cell leukemia\/lymphoma virus transformation. 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