{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:05:45Z","timestamp":1790089545199,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Platinum\u2010based chemotherapy remains a cornerstone of glioma treatment, yet resistance driven by the Fanconi anaemia (FA) DNA repair pathway limits efficacy. Here, we identified betulinic acid (BA) as a potent inhibitor of FA pathway activation. BA pretreatment abrogated cisplatin\u2010induced monoubiquitination of FANCI\/FANCD2 and disrupted their nuclear foci formation and interactions with downstream repair proteins (ERCC1, REV1 and BRCA1), leading to persistent DNA interstrand crosslinks without affecting intrastrand lesion repair. Biochemical analyses revealed that BA selectively suppressed UBE2T expression at the transcriptional level, without altering mRNA stability or protein degradation, thereby blocking the FANCL\u2010UBE2T\u2010mediated ID2 monoubiquitination cascade. In\u00a0vivo, BA significantly enhanced the antitumour efficacy of cisplatin in xenograft models. Mechanistically, BA inhibited MAPK\/ERK signalling, and pharmacological reactivation of ERK reversed BA\u2010induced suppression of UBE2T and tumour growth. Collectively, these findings uncover a previously unrecognised MAPK\/ERK\u2010UBE2T\u2010FA axis in glioma and highlight BA as a potential adjuvant to overcome cisplatin resistance through transcriptional repression of UBE2T.<\/jats:p>","DOI":"10.1111\/jcmm.71000","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:15:39Z","timestamp":1767590139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Betulinic Acid Suppresses\n                    <scp>UBE2T<\/scp>\n                    Expression via\n                    <scp>MAPK<\/scp>\n                    \/\n                    <scp>ERK<\/scp>\n                    Inhibition to Block\n                    <scp>FANCI<\/scp>\n                    and\n                    <scp>FANCD2<\/scp>\n                    Monoubiquitination in Glioblastoma"],"prefix":"10.1111","volume":"30","author":[{"given":"Yifeng","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Neurosurgery Huashan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8165-2945","authenticated-orcid":false,"given":"Maode","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Center of Brain Science The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.cell.2024.11.002","article-title":"Characterizing and Targeting Glioblastoma Neuron\u2010Tumor Networks With Retrograde Tracing","volume":"188","author":"Tetzlaff S. 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