{"doi":"10.1091/mbc.e07-05-0517","title":"Use of the Novel Plk1 Inhibitor ZK-Thiazolidinone to Elucidate Functions of Plk1 in Early and Late Stages of Mitosis","abstract":"<jats:p> Polo-like kinase 1 (Plk1) is a key regulator of mitotic progression and cell division in eukaryotes. It is highly expressed in tumor cells and considered a potential target for cancer therapy. Here, we report the discovery and application of a novel potent small-molecule inhibitor of mammalian Plk1, ZK-Thiazolidinone (TAL). We have extensively characterized TAL in vitro and addressed TAL specificity within cells by studying Plk1 functions in sister chromatid separation, centrosome maturation, and spindle assembly. Moreover, we have used TAL for a detailed analysis of Plk1 in relation to PICH and PRC1, two prominent interaction partners implicated in spindle assembly checkpoint function and cytokinesis, respectively. Specifically, we show that Plk1, when inactivated by TAL, spreads over the arms of chromosomes, resembling the localization of its binding partner PICH, and that both proteins are mutually dependent on each other for correct localization. Finally, we show that Plk1 activity is essential for cleavage furrow formation and ingression, leading to successful cytokinesis. </jats:p>","journal":"Molecular Biology of the Cell","year":2007,"id":42143,"datarank":9.434847646542414,"base_score":5.293304824724492,"endowment":5.293304824724492,"self_citation_contribution":0.793995723708674,"citation_network_contribution":8.64085192283374,"self_endowment_contribution":0.793995723708674,"citer_contribution":8.64085192283374,"corpus_percentile":null,"corpus_rank":null,"citation_count":198,"citer_count":182,"citers_with_citation_signal":154,"citers_with_endowment":154,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":42.5,"fair_percentile":4.5988586774085265,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":202100,"name":"Rüdiger Neef","orcid":null,"position":1,"is_corresponding":false},{"id":202101,"name":"Uwe Eberspächer","orcid":null,"position":2,"is_corresponding":false},{"id":202102,"name":"Knut Eis","orcid":null,"position":3,"is_corresponding":false},{"id":202103,"name":"Manfred Husemann","orcid":null,"position":4,"is_corresponding":false},{"id":202104,"name":"Dominik Mumberg","orcid":null,"position":5,"is_corresponding":false},{"id":202105,"name":"Stefan Prechtl","orcid":null,"position":6,"is_corresponding":false},{"id":122681,"name":"Volker Schulze","orcid":null,"position":7,"is_corresponding":false},{"id":202106,"name":"Gerhard Siemeister","orcid":null,"position":8,"is_corresponding":false},{"id":36794,"name":"Lars Wortmann","orcid":"0000-0001-6514-947X","position":9,"is_corresponding":false},{"id":201642,"name":"Francis A. Barr","orcid":null,"position":10,"is_corresponding":false},{"id":138892,"name":"Erich A. Nigg","orcid":null,"position":11,"is_corresponding":false},{"id":202099,"name":"Anna Santamaria","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.293304824724492,"endowment":5.293304824724492,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17671160","pmcid":"PMC1995727","openalex_id":"https://openalex.org/W2023742279","authors":[],"funders":[],"total_grants":0,"fwci":9.646,"citation_percentile":0.98910726,"influential_citations":10,"citation_trend":[{"year":2012,"count":24},{"year":2013,"count":11},{"year":2014,"count":11},{"year":2015,"count":13},{"year":2016,"count":7},{"year":2017,"count":3},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":7},{"year":2025,"count":7}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc1995727?pdf=render","host_type":"GREEN"},{"url":"https://doi.org/10.1091/mbc.e07-05-0517","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17671160","host_type":"repository"},{"url":"http://edoc.mpg.de/328367","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1995727","host_type":"repository"},{"url":"http://hdl.handle.net/11858/00-001M-0000-0010-5F09-D","host_type":"repository"}],"fields_of_study":["Microtubule and mitosis dynamics","Ubiquitin and proteasome pathways","Genomics and Chromatin Dynamics","Biology","Medicine","Chemistry","Anaphase","Aniline Compounds","Animals","Cell Cycle Proteins","Cell Line, Tumor","Centrosome","Chromatids","Cytokinesis","DNA Helicases","Enzyme Activation","Humans","Mice","Mitosis","Mitotic Index","Protein Kinase Inhibitors","Protein Serine-Threonine Kinases","Proto-Oncogene Proteins","Spindle Apparatus","Thiazolidines","Polo-Like Kinase 1"],"mesh_terms":["Polo-Like Kinase 1","Anaphase","Aniline Compounds","Animals","Chromatids","DNA Helicases","Enzyme Activation","Humans","Mitosis","Mitotic Index","Spindle Apparatus","Proto-Oncogene Proteins","Protein Serine-Threonine Kinases","Centrosome","Cell Cycle Proteins","Cell Line, Tumor","Protein Kinase Inhibitors","Cytokinesis","Mice","Thiazolidines"],"keywords":["PLK1","Cytokinesis","Biology","Centrosome","Midbody","Mitosis","Polo-like kinase","Cell biology","Multipolar spindles","Spindle checkpoint","Mitotic 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