biostudies-literatureYang ZZGuangdong Science and Technology Department (Science and Technology Department, Guangdong Province)National Natural Science Foundation of China (National Science Foundation of China)557https://www.ebi.ac.uk/biostudies/studies/S-EPMC11718263biostudies-literatureUnknown16(1)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 ubiquitinatioNature communicationsDCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.PMC11718263818721402022B15150201002020B12120300042019B0202260032023B121206001382073067Zheng YHe JHMa XTian BDeng JLu DYang BChen YXZhang YCZhan ZShi YYang ZZLiao JYYin DZhang JYZhang YZheng BHu KYan HZhou KDong YMZhu SfalseDCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.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 ubiquitinatio2025-01-01T00:00:00Z2025 Jan2026-06-01T22:02:50.714Z2026-05-23T03:08:22.134ZS-EPMC117182633978898010.1038/s41467-025-55851-9