{"doi":"10.1038/celldisc.2016.49","title":"Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase","abstract":"<jats:title>Abstract</jats:title><jats:p>Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear. Here we show that knockout, inhibition or blockade of the nuclear entry of Aurora-A severely decreased the centromere localization of Aurora-B and the phosphorylation of histone H3 threonine 3 (H3T3-ph) mediated by the kinase Haspin in late G2 phase. We further reveal that nuclear-accumulated Aurora-A phosphorylates Haspin at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex. In addition, Aurora-A facilitates the association of Aurora-B with their common substrates: Haspin and Plk1. Notably, these functions of Aurora-A are mostly independent of Plk1. Thus we demonstrate that, in late G2 and prophase, Aurora-A phosphorylates Haspin to trigger the Haspin-H3T3-ph-Aurora-B positive feedback loop that supports the timely establishment of the chromosomal passenger complex and the mitotic checkpoint before spindle assembly.</jats:p>","journal":"Cell Discovery","year":2017,"id":42459,"datarank":1.449140045222122,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.9116122044537053,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.9116122044537053,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":25,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":203202,"name":"Ya Jiang","orcid":null,"position":1,"is_corresponding":false},{"id":203203,"name":"Lucy Lu","orcid":null,"position":2,"is_corresponding":false},{"id":203204,"name":"Mimi Cao","orcid":null,"position":3,"is_corresponding":false},{"id":203205,"name":"Yulong Qiao","orcid":null,"position":4,"is_corresponding":false},{"id":58796,"name":"Xing Liu","orcid":"0000-0002-7480-5085","position":5,"is_corresponding":false},{"id":149633,"name":"Dan Liu","orcid":null,"position":6,"is_corresponding":false},{"id":203206,"name":"Terry Van Dyke","orcid":null,"position":7,"is_corresponding":false},{"id":203207,"name":"Fangwei Wang","orcid":null,"position":8,"is_corresponding":false},{"id":202639,"name":"Xuebiao Yao","orcid":null,"position":9,"is_corresponding":false},{"id":86584,"name":"Jing Guo","orcid":null,"position":10,"is_corresponding":false},{"id":203208,"name":"Zhenye Yang","orcid":null,"position":11,"is_corresponding":false},{"id":203201,"name":"Fazhi Yu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.58351893845611,"endowment":3.58351893845611,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28101375","pmcid":"PMC5223110","openalex_id":"https://openalex.org/W2569442203","authors":[],"funders":[],"total_grants":0,"fwci":1.3913,"citation_percentile":0.78652165,"influential_citations":1,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":4},{"year":2020,"count":2},{"year":2021,"count":8},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":6},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/celldisc201649.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/celldisc201649.pdf","host_type":"GOLD"},{"url":"https://www.nature.com/articles/celldisc201649.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/celldisc201649","host_type":"publisher"},{"url":"https://doi.org/10.1038/celldisc.2016.49","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28101375","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5223110","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5223110","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5223110?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Microtubule and mitosis dynamics","Ubiquitin and proteasome pathways","Cellular Mechanics and Interactions","Medicine","Biology"],"mesh_terms":[],"keywords":["Loop (graph theory)","Spindle checkpoint","Phase (matter)","Meiosis","Physics","Computer science","Biology","Mathematics","Kinetochore","Genetics","Aurora-A","Spindle Assembly Checkpoint","Chromosomal Passenger Complex","Haspin","H3t3-ph"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"No poverty"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-14T03:05:15.964499Z","pmid":null,"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":[]}