{"doi":"10.26508/lsa.202201726","title":"AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation","abstract":"<jats:p>The AurkA kinase is a well-known mitotic regulator, frequently overexpressed in tumors. The microtubule-binding protein TPX2 controls AurkA activity, localization, and stability in mitosis. Non-mitotic roles of AurkA are emerging, and increased nuclear localization in interphase has been correlated with AurkA oncogenic potential. Still, the mechanisms leading to AurkA nuclear accumulation are poorly explored. Here, we investigated these mechanisms under physiological or overexpression conditions. We observed that AurkA nuclear localization is influenced by the cell cycle phase and nuclear export, but not by its kinase activity. Importantly, AURKA overexpression is not sufficient to determine its accumulation in interphase nuclei, which is instead obtained when AURKA and TPX2 are co-overexpressed or, to a higher extent, when proteasome activity is impaired. Expression analyses show that AURKA, TPX2, and the import regulator CSE1L are co-overexpressed in tumors. Finally, using MCF10A mammospheres we show that TPX2 co-overexpression drives protumorigenic processes downstream of nuclear AurkA. We propose that AURKA/TPX2 co-overexpression in cancer represents a key determinant of AurkA nuclear oncogenic functions.</jats:p>","journal":"Life Science Alliance","year":2023,"id":645728,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1681534,"name":"Federica Polverino","orcid":null,"position":1,"is_corresponding":false},{"id":1681535,"name":"Venturina Stagni","orcid":null,"position":2,"is_corresponding":false},{"id":1681537,"name":"Valentina Sterbini","orcid":null,"position":3,"is_corresponding":false},{"id":1681539,"name":"Camilla Ascanelli","orcid":"0000-0002-6266-2822","position":4,"is_corresponding":false},{"id":1681540,"name":"Francesco Davide Naso","orcid":null,"position":5,"is_corresponding":false},{"id":1681541,"name":"Anna Mastrangelo","orcid":null,"position":6,"is_corresponding":false},{"id":1176989,"name":"Alessandro Rosa","orcid":"0000-0001-9999-7223","position":7,"is_corresponding":false},{"id":1681542,"name":"Alessandro Paiardini","orcid":"0000-0001-9078-7545","position":8,"is_corresponding":false},{"id":1681543,"name":"Catherine Lindon","orcid":"0000-0003-3554-2574","position":9,"is_corresponding":false},{"id":202424,"name":"Giulia Guarguaglini","orcid":"0000-0002-7541-8183","position":10,"is_corresponding":false},{"id":202422,"name":"Italia Anna Asteriti","orcid":"0000-0002-6582-5500","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation","abstract":"<jats:p>The AurkA kinase is a well-known mitotic regulator, frequently overexpressed in tumors. The microtubule-binding protein TPX2 controls AurkA activity, localization, and stability in mitosis. Non-mitotic roles of AurkA are emerging, and increased nuclear localization in interphase has been correlated with AurkA oncogenic potential. Still, the mechanisms leading to AurkA nuclear accumulation are poorly explored. Here, we investigated these mechanisms under physiological or overexpression conditions. We observed that AurkA nuclear localization is influenced by the cell cycle phase and nuclear export, but not by its kinase activity. Importantly, AURKA overexpression is not sufficient to determine its accumulation in interphase nuclei, which is instead obtained when AURKA and TPX2 are co-overexpressed or, to a higher extent, when proteasome activity is impaired. Expression analyses show that AURKA, TPX2, and the import regulator CSE1L are co-overexpressed in tumors. Finally, using MCF10A mammospheres we show that TPX2 co-overexpression drives protumorigenic processes downstream of nuclear AurkA. We propose that AURKA/TPX2 co-overexpression in cancer represents a key determinant of AurkA nuclear oncogenic functions.</jats:p>","is_dataset_classified":null,"base_score":3.044522437723423,"endowment":3.044522437723423,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36797043","pmcid":"PMC9936162","openalex_id":"https://openalex.org/W4321055739","authors":[],"funders":[{"funder_name":"Associazione Italiana per la Ricerca sul Cancro","grant_id":"IG-2021 ID: 25648","title":null},{"funder_name":"Associazione Italiana per la Ricerca sul Cancro","grant_id":"MFAG-2017 ID:20447","title":null},{"funder_name":"Regione Lazio","grant_id":"Progetti Gruppi di Ricerca 2020 ID: A0375-2020-36597","title":null},{"funder_name":"Royal Society","grant_id":"International Exchange Grant IES/R3/170195","title":null},{"funder_name":"UKRI | Biotechnology and Biological Sciences Research Council","grant_id":"BB/R004137/1","title":"Translating the ubiquitin code in mitotic cells"},{"funder_name":"AstraZeneca","grant_id":"","title":null}],"total_grants":6,"fwci":2.6145,"citation_percentile":0.90258382,"influential_citations":0,"citation_trend":[{"year":2023,"count":2},{"year":2024,"count":7},{"year":2025,"count":7},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.life-science-alliance.org/content/lsa/6/5/e202201726.full.pdf","host_type":"journal"},{"url":"https://www.life-science-alliance.org/content/lsa/6/5/e202201726.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.26508/lsa.202201726","host_type":"publisher"},{"url":"https://doi.org/10.26508/lsa.202201726","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36797043","host_type":"repository"},{"url":"https://hdl.handle.net/11573/1670054","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9936162","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/347736","host_type":"repository"},{"url":"https://doaj.org/article/718653b43a1842d38ab07bbde0a427fe","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.95153","host_type":"repository"},{"url":"https://iris.uniroma1.it/bitstream/11573/1670054/1/Asteriti_AurkA_2023.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9936162/pdf/LSA-2022-01726.pdf","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/bitstreams/9ba3f903-6fd6-4879-bd8f-b394ba6c67dd/download","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9936162","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9936162?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.17863/cam.95153","host_type":""},{"url":"http://dx.doi.org/10.26508/lsa.202201726","host_type":""},{"url":"https://hdl.handle.net/20.500.14243/510095","host_type":""}],"fields_of_study":["Microtubule and mitosis dynamics","Nuclear Structure and Function","DNA Repair Mechanisms","0301 basic medicine","0303 health sciences","03 medical and health sciences","Humans","Aurora Kinase A","Cell Cycle Proteins","Proteolysis","Microtubule-Associated Proteins","Nuclear Proteins","Neoplasms"],"mesh_terms":["Humans","Microtubule-Associated Proteins","Neoplasms","Nuclear Proteins","Cell Cycle Proteins","Proteolysis","Aurora Kinase A"],"keywords":["Nuclear transport","Nuclear localization sequence","Mitosis","Nuclear export signal","Nuclear protein","Regulator","Interphase","Cell biology","Cancer research","Kinase","Cell cycle","Phosphorylation","Proteasome","Cell nucleus","Biology","Cell","Nucleus","Gene","Transcription factor","Genetics","AurkA; TPX2; mitosis","Neoplasms","Proteolysis","Humans","Nuclear Proteins","Cell Cycle Proteins","AurkA, TPX2, AURKA/TPX2 co-overexpression, cancer","Microtubule-Associated Proteins","Research Articles","Aurora Kinase A"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T09:57:59.358962Z","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":[]}