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Ubiquitin\u2010specific protease 28 (USP28) is a deubiquitinase known to regulate the stability of NOTCH1. Here, we report that genetic depletion of USP28 or using CT1113, a potent small molecule targeting USP28, can strongly destabilize NOTCH1 and inhibit the growth of T\u2010ALL cells. Moreover, we show that USP28 also regulates the stability of sterol regulatory element binding protein 1 (SREBP1), which has been reported to mediate increased lipogenesis in tumour cells. As the most critical transcription factor involved in regulating lipogenesis, SREBP1 plays an important role in the metabolism of T\u2010ALL. Therefore, USP28 may be a potential therapeutic target, and CT1113 may be a promising novel drug for T\u2010ALL with or without mutant NOTCH1.<\/jats:p>","DOI":"10.1111\/bjh.19492","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T02:23:53Z","timestamp":1714443833000},"page":"2301-2318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preclinical testing of <scp>CT1113<\/scp>, a novel <scp>USP28<\/scp> inhibitor, for the treatment of T\u2010cell acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"204","author":[{"given":"Jieyu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"},{"name":"Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy Zhejiang University  Hangzhou Zhejiang China"},{"name":"Liangzhu Laboratory Zhejiang University 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