title: Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5.
abstract: Whether transcriptional regulators are functionally involved in mitosis is a fundamental question in cell biology. Here we report that the RNF20/40 complex, a major ubiquitin ligase catalysing histone H2B monoubiquitination, interacts with the motor protein Eg5 during mitosis and participates in spindle assembly. We show that the RNF20/40 complex monoubiquitinates and stabilizes Eg5. Loss of RNF20/40 results in spindle assembly defects, cell cycle arrest and apoptosis. Consistently, depletion of either RNF20/40 or Eg5 suppresses breast cancer in vivo. Significantly, RNF20/40 and Eg5 are concurrently upregulated in human breast carcinomas and high Eg5 expression is associated with poorer overall survival of patients with luminal A, or B, breast cancer. Our study uncovers an important spindle assembly role of the RNF20/40 complex, and implicates the RNF20/40-Eg5 axis in breast carcinogenesis, supporting the pursuit of these proteins as potential targets for breast cancer therapeutic interventions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Huo
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumour Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Su
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.|Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chenghao
authors.initials: C
authors.lastname: Xuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D055162:Biocatalysis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D000073658:Loss of Function Mutation; D008239:Lysine / Q000378:metabolism; D061986:MCF-7 Cells; D008819:Mice, Nude; D008938:Mitosis; D011485:Protein Binding; D055550:Protein Stability; D015398:Signal Transduction / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*; D064047:Spindle Poles / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C470243:KIF11 protein, human; C506646:RNF20 protein, human; C413363:RNF40 protein, human; D044767:Ubiquitin-Protein Ligases; D016547:Kinesins; D008239:Lysine