{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:26:24Z","timestamp":1787635584419,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>\n                    Transcription factor RUNX1 plays important roles in hematopoiesis and leukemogenesis. RUNX1 function is tightly controlled through posttranslational modifications, including ubiquitination and acetylation. However, its regulation via ubiquitination, especially proteasome\u2010independent ubiquitination, is poorly understood. We previously identified DTX2 as a RUNX1\u2010interacting E3 ligase using a cell\u2010free AlphaScreen assay. In this study, we examined whether DTX2 is involved in the regulation of RUNX1 using\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex\u2009vivo<\/jats:italic>\n                    analyses. DTX2 bound to RUNX1 and other RUNX family members RUNX2 and RUNX3 through their C\u2010terminal region. DTX2\u2010induced RUNX1 ubiquitination did not result in RUNX1 protein degradation. Instead, we found that the acetylation of RUNX1, which is known to enhance the transcriptional activity of RUNX1, was inhibited in the presence of DTX2. Concomitantly, DTX2 reduced the RUNX1\u2010induced activation of an MCSFR luciferase reporter. We also found that DTX2 induced RUNX1 cytoplasmic mislocalization. Moreover, DTX2 overexpression showed a substantial growth\u2010inhibitory effect in RUNX1\u2010dependent leukemia cell lines. Thus, our findings indicate a novel aspect of the ubiquitination and acetylation of RUNX1 that is modulated by DTX2 in a proteosome\u2010independent manner.\n                  <\/jats:p>","DOI":"10.1111\/febs.16914","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T19:54:05Z","timestamp":1690487645000},"page":"5141-5157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The E3 ligase DTX2 inhibits RUNX1 function by binding its C terminus and prevents the growth of RUNX1\u2010dependent leukemia cells"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-9434","authenticated-orcid":false,"given":"Taishi","family":"Yonezawa","sequence":"first","affiliation":[{"name":"Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  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