{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:30:14Z","timestamp":1791045014875,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T00:00:00Z","timestamp":1279152000000},"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":[[2010,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human T-lymphotropic virus 1 (HTLV-1) causes an aggressive malignancy of T lymphocytes called adult T-cell leukemia\/lymphoma (ATLL), and expression of HTLV-1 Tax influences cell survival, proliferation, and genomic stability in the infected T lymphocytes. Cyclin-dependent kinase inhibitor 1A (CDKN1A\/p21\n            <jats:sup>waf1\/Cip1<\/jats:sup>\n            ) is upregulated by Tax, without perturbation of cell cycle control. During an analysis of the gene expression profiles of ATLL cells, we found very low expression of\n            <jats:italic>CDKN1A<\/jats:italic>\n            in ATLL-derived cell lines and ATLL cells from patient samples, and epigenetic abnormalities including promoter methylation are one of the mechanisms for the low\n            <jats:italic>CDKN1A<\/jats:italic>\n            expression in ATLL cells. Three HTLV-1-infected cell lines showed high levels of expression of both\n            <jats:italic>CDKN1A<\/jats:italic>\n            and\n            <jats:italic>Tax<\/jats:italic>\n            , but expression of\n            <jats:italic>CDKN1A<\/jats:italic>\n            was detected in only two of six ATLL-derived cell lines. In both the HTLV-1-infected and ATLL cell lines, we found that activated Akt phosphorylates CDKN1A at threonine 145 (T145), leading to cytoplasmic localization of CDKNIA. In HTLV-1-infected cell lines, cytoplasmic CDKN1A did not inhibit the cell cycle after UV irradiation; however, following treatment with LY294002, a PI3K inhibitor, CDKN1A was dephosphorylated and relocalized to the nucleus, resulting in suppression of the cell cycle. In the ATLL cell lines, treatment with LY294002 did not inhibit the cell cycle but induced apoptosis with the cytoplasmic localization. Therefore, the low\n            <jats:italic>CDKN1A<\/jats:italic>\n            expression in ATLL cells may be a key player in ATLL leukemogenesis, and the abnormal genomic methylation may influence the expression of not only HTLV-1\n            <jats:italic>Tax<\/jats:italic>\n            but also\n            <jats:italic>CDKN1A<\/jats:italic>\n            during long-term development of ATLL from the HTLV-1-infected T lymphocytes.\n          <\/jats:p>","DOI":"10.1128\/jvi.00073-10","type":"journal-article","created":{"date-parts":[[2010,5,6]],"date-time":"2010-05-06T01:34:59Z","timestamp":1273109699000},"page":"6966-6977","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Downregulation of CDKN1A in Adult T-Cell Leukemia\/Lymphoma despite Overexpression of CDKN1A in Human T-Lymphotropic Virus 1-Infected Cell Lines"],"prefix":"10.1128","volume":"84","author":[{"given":"Masaaki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Nakahata","sequence":"additional","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Kawano","sequence":"additional","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Umeki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Okayama","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Morishita","sequence":"additional","affiliation":[{"name":"Division of Tumor and Cellular Biochemistry, Department of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.11.4243.bloodjournal86114243"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202567"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206814"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/08892220050193164"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.16.7270-7283.2000"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01149-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v8.i3.400"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806325200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202405"},{"key":"e_1_3_2_11_2","first-page":"383","volume":"112","year":"2008","unstructured":"Hidaka, T., S. 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