{"doi":"10.1073/pnas.081076898","title":"Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints","abstract":"<jats:p>Metaphase checkpoint controls sense abnormalities of chromosome\n alignment during mitosis and prevent progression to anaphase until\n proper alignment has been attained. A number of proteins, including\n mad2, bub1, and bubR1, have been implicated in the metaphase checkpoint\n control in mammalian cells. Metaphase checkpoints have been shown, in\n various systems, to read loss of either spindle tension or microtubule\n attachment at the kinetochore. Characteristically, HeLa cells arrest in\n metaphase in response to low levels of microtubule inhibitors that\n leave an intact spindle and a metaphase plate. Here we show that the\n arrest induced by nanomolar vinblastine correlates with loss of tension\n at the kinetochore, and that in response the checkpoint proteins bub1\n and bubR1 are recruited to the kinetochore but mad2 is not. mad2\n remains competent to respond and is recruited at higher drug doses that\n disrupt spindle association with the kinetochores. Further, although\n mad2 forms a complex with cdc20, it does not associate with bub1 or\n bubR1. We conclude that mammalian bub1/bubR1 and mad2 operate as\n elements of distinct pathways sensing tension and attachment,\n respectively.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2001,"id":659362,"datarank":0.8441431670535957,"base_score":5.627621113690637,"endowment":5.627621113690637,"self_citation_contribution":0.8441431670535957,"citation_network_contribution":0.0,"self_endowment_contribution":0.8441431670535957,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":277,"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":586778,"name":"Paul R. Andreassen","orcid":"0000-0002-9760-1595","position":1,"is_corresponding":false},{"id":1721198,"name":"Françoise B. Lacroix","orcid":null,"position":2,"is_corresponding":false},{"id":659710,"name":"Leslie Wilson","orcid":"0000-0002-3305-8730","position":3,"is_corresponding":false},{"id":1609274,"name":"Robert L. Margolis","orcid":null,"position":4,"is_corresponding":false},{"id":1447024,"name":"Dimitrios A. Skoufias","orcid":"0000-0001-5595-3413","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints","abstract":"<jats:p>Metaphase checkpoint controls sense abnormalities of chromosome\n alignment during mitosis and prevent progression to anaphase until\n proper alignment has been attained. A number of proteins, including\n mad2, bub1, and bubR1, have been implicated in the metaphase checkpoint\n control in mammalian cells. Metaphase checkpoints have been shown, in\n various systems, to read loss of either spindle tension or microtubule\n attachment at the kinetochore. Characteristically, HeLa cells arrest in\n metaphase in response to low levels of microtubule inhibitors that\n leave an intact spindle and a metaphase plate. Here we show that the\n arrest induced by nanomolar vinblastine correlates with loss of tension\n at the kinetochore, and that in response the checkpoint proteins bub1\n and bubR1 are recruited to the kinetochore but mad2 is not. mad2\n remains competent to respond and is recruited at higher drug doses that\n disrupt spindle association with the kinetochores. Further, although\n mad2 forms a complex with cdc20, it does not associate with bub1 or\n bubR1. We conclude that mammalian bub1/bubR1 and mad2 operate as\n elements of distinct pathways sensing tension and attachment,\n respectively.</jats:p>","is_dataset_classified":null,"base_score":5.627621113690637,"endowment":5.627621113690637,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11274370","pmcid":"PMC31862","openalex_id":"https://openalex.org/W2074955549","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS013560","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS13560","title":null}],"total_grants":2,"fwci":8.8214,"citation_percentile":0.98598051,"influential_citations":0,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":15},{"year":2014,"count":6},{"year":2015,"count":8},{"year":2016,"count":6},{"year":2017,"count":4},{"year":2018,"count":6},{"year":2019,"count":9},{"year":2020,"count":2},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2025,"count":1},{"year":2026,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/31862","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/31862","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.081076898","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.081076898","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11274370","host_type":"repository"}],"fields_of_study":["Microtubule and mitosis dynamics","Ubiquitin and proteasome pathways","Plant Molecular Biology Research","Blotting, Western","Calcium-Binding Proteins","Cell Cycle Proteins","HeLa Cells","Humans","Mad2 Proteins","Microinjections","Microscopy, Fluorescence","Precipitin Tests","Protein Kinases","Protein Serine-Threonine Kinases","Repressor Proteins"],"mesh_terms":["Calcium-Binding Proteins","HeLa Cells","Humans","Microinjections","Microscopy, Fluorescence","Precipitin Tests","Protein Kinases","Repressor Proteins","Blotting, Western","Protein Serine-Threonine Kinases","Cell Cycle Proteins","Mad2 Proteins","Hela Cells"],"keywords":["Mad2","BUB1","Kinetochore","Spindle checkpoint","Metaphase","Cell biology","Biology","Anaphase","Mitosis","Spindle apparatus","Aurora B kinase","Genetics","Chromosome","Cell cycle","Cell division","Cell"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T06:43:54.735376Z","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":[]}