{"doi":"10.1016/j.molcel.2025.01.008","title":"SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis","abstract":"Impairment of ribosome biogenesis (RiBi) triggered by inhibition of ribosomal RNA (rRNA) synthesis and processing leads to various biological effects. We report that Schlafen 11 (SLFN11) induces TP53-independent apoptosis through RiBi impairment. Upon replication stress, SLFN11 inhibits rRNA synthesis with RNA polymerase I accumulation and increased chromatin accessibility in the ribosomal DNA (rDNA) genes. SLFN11-dependent RiBi impairment preferentially depletes short-lived proteins, particularly MCL1, leading to apoptosis in response to replication stress. SLFN11's Walker B motif (E669), DNA-binding site (K652), dephosphorylation site for single-strand DNA binding (S753), and RNase sites (E209/E214) are all required for the SLFN11-mediated RiBi impairment. Comparable effects were obtained with direct RNA polymerase I inhibitors and other RiBi inhibitory conditions regardless of SLFN11. These findings were extended across 34 diverse human cancer cell lines. Thus, we demonstrate that RiBi impairment is a robust inactivator of MCL1 and an additional proapoptotic mechanism by which SLFN11 sensitizes cancer cells to chemotherapeutic agents.","journal":"Molecular Cell","year":2025,"id":509536,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1162319,"name":"Keiichi Izumikawa","orcid":"0000-0001-7262-5403","position":1,"is_corresponding":false},{"id":1363666,"name":"Sota Tate","orcid":"0000-0001-7050-4560","position":2,"is_corresponding":false},{"id":1363667,"name":"Sho Isoyama","orcid":"0000-0001-6751-1233","position":3,"is_corresponding":false},{"id":1364419,"name":"Mori Masaru","orcid":null,"position":4,"is_corresponding":false},{"id":1364420,"name":"Kohei Fujiwara","orcid":null,"position":5,"is_corresponding":false},{"id":1364421,"name":"Soyoka Watanabe","orcid":null,"position":6,"is_corresponding":false},{"id":1364422,"name":"Takayuki Ohga","orcid":null,"position":7,"is_corresponding":false},{"id":7159,"name":"Ukhyun Jo","orcid":"0000-0002-2826-1355","position":8,"is_corresponding":false},{"id":326930,"name":"Daiki Taniyama","orcid":"0000-0001-5388-4581","position":9,"is_corresponding":false},{"id":1363668,"name":"Shojiro Kitajima","orcid":"0000-0002-4000-0473","position":10,"is_corresponding":false},{"id":1364423,"name":"Soichiro Tanaka","orcid":null,"position":11,"is_corresponding":false},{"id":1363669,"name":"Hiroshi Onji","orcid":"0000-0001-5778-0149","position":12,"is_corresponding":false},{"id":49186,"name":"Shun‐Ichiro Kageyama","orcid":"0000-0002-6072-0144","position":13,"is_corresponding":false},{"id":1364424,"name":"Gaku Yamamoto","orcid":null,"position":14,"is_corresponding":false},{"id":1363670,"name":"Hitoshi Saito","orcid":"0000-0002-7986-0913","position":15,"is_corresponding":false},{"id":1363671,"name":"Tomoko Morita","orcid":"0009-0004-9583-2471","position":16,"is_corresponding":false},{"id":335168,"name":"Masayasu Okada","orcid":"0000-0002-9151-8184","position":17,"is_corresponding":false},{"id":335167,"name":"Manabu Natsumeda","orcid":"0000-0003-3098-8323","position":18,"is_corresponding":false},{"id":825873,"name":"Masami Nagahama","orcid":"0000-0001-6763-8058","position":19,"is_corresponding":false},{"id":1363672,"name":"Junya Kobayashi","orcid":"0000-0003-4645-7500","position":20,"is_corresponding":false},{"id":551708,"name":"Akihiro Ohashi","orcid":"0000-0002-4036-9385","position":21,"is_corresponding":false},{"id":483350,"name":"Hiroyuki Sasanuma","orcid":"0000-0003-2824-4499","position":22,"is_corresponding":false},{"id":546741,"name":"Shigeki Higashiyama","orcid":"0000-0002-2417-3921","position":23,"is_corresponding":false},{"id":1363673,"name":"Shingo Dan","orcid":"0000-0002-0022-2725","position":24,"is_corresponding":false},{"id":232027,"name":"Yves Pommier","orcid":"0000-0002-3108-0758","position":25,"is_corresponding":false},{"id":291709,"name":"Junko Murai","orcid":"0000-0003-2023-6160","position":26,"is_corresponding":false},{"id":1364418,"name":"Akane Ogawa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T02:47:24.513904Z","pmid":"39909041","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}