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DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer

Author

Listed:
  • Zhi-Zhi Yang

    (Sun Yat-sen University)

  • Bing Yang

    (Sun Yat-sen University)

  • Haiyan Yan

    (Sun Yat-sen University)

  • Xingyu Ma

    (Sun Yat-sen University)

  • Bin Tian

    (Sun Yat-sen University)

  • Bingqi Zheng

    (Sun Yat-sen University)

  • Yong-Xian Chen

    (Sun Yat-sen University)

  • Yi-Ming Dong

    (Sun Yat-sen University)

  • Jinsi Deng

    (Sun Yat-sen University)

  • Ziling Zhan

    (Sun Yat-sen University)

  • Yanmei Shi

    (Sun Yat-sen University)

  • Jing Yuan Zhang

    (Sun Yat-sen University)

  • Daning Lu

    (Sun Yat-sen University)

  • Jie-Hua He

    (Sun Yat-sen University)

  • Yin Zhang

    (Sun Yat-sen University)

  • KaiShun Hu

    (Sun Yat-sen University)

  • Shuang Zhu

    (Guangdong Pharmaceutical University)

  • Keda Zhou

    (the University of Hong Kong)

  • Yu-Chan Zhang

    (Sun Yat-Sen University)

  • Yiqing Zheng

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Dong Yin

    (Sun Yat-sen University)

  • Jian-You Liao

    (Sun Yat-sen University
    Sun Yat-sen University)

Abstract

Hyperactivation of ribosome biogenesis (RiBi) drives cancer progression, yet the role of RiBi-associated proteins (RiBPs) in breast cancer (BC) is underexplored. In this study, we perform a comprehensive multi-omics analysis and reveal that assembly and maturation factors (AMFs), a subclass of RiBPs, are upregulated at both RNA and protein levels in BC, correlating with poor patient outcomes. In contrast, ribosomal proteins (RPs) do not show systematic upregulation across various cancers, including BC. We further demonstrate that the oncogenic activation of a top AMF candidate in BC, DCAF13, enhances Pol I transcription and promotes proliferation in BC cells both in vitro and in vivo. Mechanistically, DCAF13 promotes Pol I transcription activity by facilitating the K63-linked ubiquitination of RPA194. This process stimulates global protein synthesis and cell growth. Our findings uncover a modification of RPA194 that regulates Pol I activity; this modification is dysregulated in BC, contributing to cancer progression.

Suggested Citation

  • Zhi-Zhi Yang & Bing Yang & Haiyan Yan & Xingyu Ma & Bin Tian & Bingqi Zheng & Yong-Xian Chen & Yi-Ming Dong & Jinsi Deng & Ziling Zhan & Yanmei Shi & Jing Yuan Zhang & Daning Lu & Jie-Hua He & Yin Zha, 2025. "DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55851-9
    DOI: 10.1038/s41467-025-55851-9
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