DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer
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...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55851-9 |
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| author | 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 Zhang KaiShun Hu Shuang Zhu Keda Zhou Yu-Chan Zhang Yiqing Zheng Dong Yin Jian-You Liao |
| author_facet | 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 Zhang KaiShun Hu Shuang Zhu Keda Zhou Yu-Chan Zhang Yiqing Zheng Dong Yin Jian-You Liao |
| author_sort | Zhi-Zhi Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-07c3ee03e6884cebb734d874210c0144 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-07c3ee03e6884cebb734d874210c01442025-01-12T12:30:03ZengNature PortfolioNature Communications2041-17232025-01-0116111910.1038/s41467-025-55851-9DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast CancerZhi-Zhi Yang0Bing Yang1Haiyan Yan2Xingyu Ma3Bin Tian4Bingqi Zheng5Yong-Xian Chen6Yi-Ming Dong7Jinsi Deng8Ziling Zhan9Yanmei Shi10Jing Yuan Zhang11Daning Lu12Jie-Hua He13Yin Zhang14KaiShun Hu15Shuang Zhu16Keda Zhou17Yu-Chan Zhang18Yiqing Zheng19Dong Yin20Jian-You Liao21Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Clinical Laboratory, Shenshan Central Hospital, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityCenter for Bioresources and Drug Discovery and School of Biosciences and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical UniversitySchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, the University of Hong KongGuangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory for Biocontrol, School of Life Science, Sun Yat-Sen UniversityCenter for Precision Medicine, Shenshan Central Hospital, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract 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.https://doi.org/10.1038/s41467-025-55851-9 |
| spellingShingle | 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 Zhang KaiShun Hu Shuang Zhu Keda Zhou Yu-Chan Zhang Yiqing Zheng Dong Yin Jian-You Liao DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer Nature Communications |
| title | DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer |
| title_full | DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer |
| title_fullStr | DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer |
| title_full_unstemmed | DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer |
| title_short | DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer |
| title_sort | dcaf13 mediated k63 linked ubiquitination of rna polymerase i promotes uncontrolled proliferation in breast cancer |
| url | https://doi.org/10.1038/s41467-025-55851-9 |
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