{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:41:29Z","timestamp":1790138489420,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Adult T\u2010cell leukemia (ATL) is an aggressive malignancy caused by human T\u2010cell leukemia virus type 1 (HTLV\u20101) infection. Enhancer of zeste homolog 2 (EZH2) has been implicated in the development and progression of multiple cancers, including virus\u2010induced malignancies. However, the potential function of EZH2 in HTLV\u20101\u2010induced oncogenesis has not been clearly elucidated. In the present study, we showed that EZH2 was overexpressed and activated in HTLV\u20101\u2010infected cell lines, potentially due to the activation of EZH2 promoter by HTLV\u20101 Tax and NF\u2010\u03baB p65 subunit. In addition, we found that EZH2 enhanced the HBZ\u2010induced activation of TGF\u2010\u03b2 signaling in a histone methyltransferase\u2010independent manner. As a mechanism for these actions, we found that EZH2 targeted Smad3\/Smad4 to form a ternary complex, and the association between Smad3 and Smad4 was markedly enhanced in the presence of EZH2. Knockdown of EZH2 in ATL cells indeed repressed the expressions of the TGF\u2010\u03b2 target genes. In particular, EZH2 synergistically enhanced the HBZ\/TGF\u2010\u03b2\u2010induced Foxp3 expression. Treatment of 3\u2010Deazaneplanocin A, a specific inhibitor of EZH2 significantly inhibited the Foxp3 expression. Taken together, our results suggest that EZH2 may be involved in the differentiation of regulatory T cells through activating the HBZ\u2010Smad3\u2010TGF\u2010\u03b2 signaling axis, which is considered to be a key strategy for viral persistence.<\/jats:p>","DOI":"10.1002\/jmv.70025","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T05:38:42Z","timestamp":1731389922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["EZH2 Activates HTLV\u20101 bZIP Factor\u2010Mediated TGF\u2010\u03b2 Signaling in Adult T\u2010Cell Leukemia"],"prefix":"10.1002","volume":"96","author":[{"given":"Xu","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University Hangzhou China"},{"name":"College of Life Sciences Zhejiang Normal University Jinhua 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