{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:48:00Z","timestamp":1791341280752,"version":"4.3.1"},"reference-count":574,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia\/lymphoma (ATL). The trans-activator protein Tax of HTLV-1 is thought to play a crucial role in the early-stage transformation of the virus-infected cells. Tax is a multi-functional protein and modulates cellular signaling pathways that promote proliferation and survival of HTLV-1-infected cells, primarily through the trans-activation of cellular target genes. Tax interacts with a variety of host cell factors including signal transducers and transcription factors, leading to the activation of transcription factors such as CREB, NF-\u03baB, and SRF and activates both its own promoter and those of a variety of host cellular genes. Tax activates its own promoter mainly through CREB and host cellular genes through NF-\u03baB, SRF, and CREB. Accumulating evidence indicates that the Tax-mediated trans-activation of target genes through NF-\u03baB plays an essential role in the transformation of HTLV-1 infected cells. However, the repertoire of Tax target genes, especially those crucial for leukemogenesis, are not known in detail. In this review, we summarize transcriptional activation mechanisms and target genes of Tax, especially focusing on transformation, to facilitate understanding of the underlying mechanisms of leukemogenesis induced by HTLV-1 infection.<\/jats:p>","DOI":"10.3390\/genes16101221","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"1221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptional Activation Mechanisms and Target Genes of the Oncogene Product Tax of Human T-Cell Leukemia Virus Type 1"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5743-7842","authenticated-orcid":false,"given":"Mashiro","family":"Shirasawa","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3222-7590","authenticated-orcid":false,"given":"Rinka","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2593-3572","authenticated-orcid":false,"given":"Yaxuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Fikriyanti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1142-4753","authenticated-orcid":false,"given":"Ritsuko","family":"Iwanaga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-571X","authenticated-orcid":false,"given":"Andrew P.","family":"Bradford","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Kurayoshi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Morphological Biology, Ohu University School of Dentistry, 31-1 Misumido Tomitamachi, Koriyama 963-8611, Fukushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. 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