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Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5

Yang Duan, Dawei Huo, Jie Gao, Heng Wu, Zheng Ye, Zhe Liu, Kai Zhang, Lin Shan, Xing Zhou, Yue Wang, Dongxue Su, Xiang Ding, Lei Shi, Yan Wang, Yongfeng Shang () and Chenghao Xuan ()
Additional contact information
Yang Duan: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Dawei Huo: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Jie Gao: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Heng Wu: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumour Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital
Zheng Ye: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Zhe Liu: Tianjin Medical University
Kai Zhang: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Lin Shan: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Xing Zhou: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Yue Wang: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Dongxue Su: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Xiang Ding: Institute of Biophysics, Chinese Academy of Sciences
Lei Shi: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Yan Wang: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Yongfeng Shang: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University
Chenghao Xuan: Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12648

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DOI: 10.1038/ncomms12648

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