{"doi":"10.1016/j.celrep.2025.115317","title":"An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity","abstract":"Cancer cells are often aneuploid and frequently display elevated rates of chromosome mis-segregation, called chromosomal instability (CIN). CIN is caused by hyperstable kinetochore-microtubule (K-MT) attachments that reduce the correction efficiency of erroneous K-MT attachments. UMK57, a chemical agonist of the protein MCAK (mitotic centromere-associated kinesin), improves chromosome segregation fidelity in CIN cancer cells by destabilizing K-MT attachments, but cells rapidly develop resistance. To determine the mechanism, we performed unbiased screens, which revealed increased phosphorylation in cells adapted to UMK57 at Aurora kinase A phosphoacceptor sites on BOD1L1 (protein biorientation defective 1-like-1). BOD1L1 depletion or Aurora kinase A inhibition eliminated resistance to UMK57. BOD1L1 localizes to spindles/kinetochores during mitosis, interacts with the PP2A phosphatase, and regulates phosphorylation levels of kinetochore proteins, chromosome alignment, mitotic progression, and fidelity. Moreover, the BOD1L1 gene is mutated in a subset of human cancers, and BOD1L1 depletion reduces cell growth in combination with clinically relevant doses of Taxol or Aurora kinase A inhibitor.","journal":"Cell Reports","year":2025,"id":517914,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"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":1045464,"name":"Irma Vlasac","orcid":"0000-0002-1037-2698","position":1,"is_corresponding":false},{"id":1385355,"name":"Tatiana Lyalina","orcid":null,"position":2,"is_corresponding":false},{"id":870222,"name":"Martin R. Higgs","orcid":"0000-0002-8218-0089","position":3,"is_corresponding":false},{"id":14596,"name":"Brock C. Christensen","orcid":"0000-0003-3022-426X","position":4,"is_corresponding":false},{"id":891484,"name":"Susanne Bechstedt","orcid":"0000-0002-4706-9975","position":5,"is_corresponding":false},{"id":399826,"name":"Duane A. Compton","orcid":"0000-0002-4445-9118","position":6,"is_corresponding":false},{"id":910530,"name":"Thomas J. Kucharski","orcid":"0000-0002-3127-5352","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:49:04.756302Z","pmid":"39970043","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":[]}