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Ubiquitin ligase dtx3 empowers mutant p53 to promote ovarian cancer development

Genes & Diseases 2022年第3期9卷 705-716页

作者： Shanshan Wang Qian Hao Jiajia Li Yajie Chen Hua Lu Xiaohua Wu Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032PR China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032PR China Department of Gynecological Oncology Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Radiation Oncology Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Biochemistry&Molecular Biology and Tulane Cancer Center Tulane University School of MedicineNew OrleansLA 70112USA Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyInstitutes of Biomedical SciencesFudan UniversityShanghai 200032PR China

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.

关键词： dtx3 E3 ubiquitin ligase Invasion Mutant p53 Ovarian cancer Proliferation

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