Ubiquitin ligase DTX3 empowers mutant p53 to promote ovarian cancer development
作者机构：Fudan University Shanghai Cancer Center and Institutes of Biomedical SciencesFudan UniversityShanghai 200032PR China Department of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032PR China Department of Gynecological OncologyFudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Radiation OncologyFudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Biochemistry&Molecular Biology and Tulane Cancer CenterTulane University School of MedicineNew OrleansLA 70112USA Key Laboratory of Breast Cancer in ShanghaiFudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Shanghai Key Laboratory of Medical EpigeneticsInternational Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyInstitutes of Biomedical SciencesFudan UniversityShanghai 200032PR China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2022年第9卷第3期
页 面：705-716页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：This study was supported by the National Natural Science Foundation of China(No.81672566,81874053,81972431,and 81702352) the Basic and Clinical Translational Research Fundi ng from Fudan University Sha nghai Cancer Center
主 题：DTX3 E3 ubiquitin ligase Invasion Mutant p53 Ovarian cancer Proliferation
摘 要：The deltex family protein DTX3 is believed to possess E3 ubiquitin ligase activity,as it contains a classic RING finger ***,its biological role and the underlying mechanism in cancer remain largely ***,we identified DTX3 as a novel mutant p53-interacting protein in ovarian ***,DTX3 mediated mutant p53 ubiqui-tination and stabilization by perturbing the MDM2-mutant p53 interaction,consequently leading to activation of *** p53 target ***,a positive correlation between the expression of DTX3 and mutant p53 target genes was further validated in ovarian *** DTX3 promoted,while depletion of DTX3 suppressed,ovarian cancer cell proliferation and ***,the pro-tumorigenic effect of DTX3 is dependent on mutant p53,because ablation of mutant p53 significantly impaired DTX3-induced gene expression and ovarian cancer cell growth and ***,DTX3 elevated the expressi on of muta nt p53 target genes and boosted ovarian tumor growth in *** ally,DTX3 was amplified and overexpressed in ovarian carci no mas,which is sign ificantly associated with unfavorable ***,our findings unveil the oncogenic role of DTX3 in ovarian cancer development by bolstering mutant p53 activity.
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