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

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  • 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
    Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center)

  • Chenghao Xuan

    (Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University)

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.

Suggested Citation

  • 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 & Chenghao Xuan, 2016. "Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12648
    DOI: 10.1038/ncomms12648
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    Cited by:

    1. Yong Geun Jeon & Hahn Nahmgoong & Jiyoung Oh & Dabin Lee & Dong Wook Kim & Jane Eunsoo Kim & Ye Young Kim & Yul Ji & Ji Seul Han & Sung Min Kim & Jee Hyung Sohn & Won Taek Lee & Sun Won Kim & Jeu Park, 2024. "Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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