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dc.contributor.authorTrakala, Marianna 
dc.contributor.authorPartida, David
dc.contributor.authorSalazar-Roa, Maria 
dc.contributor.authorMaroto, María
dc.contributor.authorWachowicz, Paulina
dc.contributor.authorde Carcer Diez, Guillermo 
dc.contributor.authorMalumbres Martinez, Marcos 
dc.date.accessioned2020-06-23T16:30:53Z
dc.date.available2020-06-23T16:30:53Z
dc.date.issued2015-10-01
dc.identifier.citationBlood . 2015;126(14):1707-14.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10543
dc.description.abstractPolyploidization in megakaryocytes is achieved by endomitosis, a specialized cell cycle in which DNA replication is followed by aberrant mitosis. Typical mitotic regulators such as Aurora kinases or Cdk1 are dispensable for megakaryocyte maturation, and inhibition of mitotic kinases may in fact promote megakaryocyte maturation. However, we show here that Polo-like kinase 1 (Plk1) is required for endomitosis, and ablation of the Plk1 gene in megakaryocytes results in defective polyploidization accompanied by mitotic arrest and cell death. Lack of Plk1 results in defective centrosome maturation and aberrant spindle pole formation, thus impairing the formation of multiple poles typically found in megakaryocytes. In these conditions, megakaryocytes arrest for a long time in mitosis and frequently die. Mitotic arrest in wild-type megakaryocytes treated with Plk1 inhibitors or Plk1-null cells is triggered by the spindle assembly checkpoint (SAC), and can be rescued in the presence of SAC inhibitors. These data suggest that, despite the dispensability of proper chromosome segregation in megakaryocytes, an endomitotic SAC is activated in these cells upon Plk1 inhibition. SAC activation results in defective maturation of megakaryocytes and cell death, thus raising a note of caution in the use of Plk1 inhibitors in therapeutic strategies based on polyploidization regulators.es_ES
dc.description.sponsorshipThis work was supported by a fellowship from the Foundation La Caixa (M.T.), and the Cell Division and Cancer group of the CNIO was funded by the Ministry of Economy and Competitiveness (SAF2012-38215), Consolider-Ingenio 2010 Programme (SAF2014-57791-REDC), Red Tematica CellSYS (BFU2014-52125-REDT), Comunidad de Madrid (OncoCycle Programme, S2010/BMD-2470), Worldwide Cancer Research (WCR #15-0278), and the MitoSys project (HEALTH-F5-2010-241548, European Union Seventh Framework Programme).
dc.language.isoenges_ES
dc.publisherAmerican Society of Hematology (ASH) es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectPOLO-LIKE KINASESes_ES
dc.subjectVOLASERTIB BI 6727es_ES
dc.subjectCELL-CYCLEes_ES
dc.subjectAURORA-Bes_ES
dc.subjectMEGAKARYOCYTE ENDOMITOSISes_ES
dc.subjectINHIBITOR VOLASERTIBes_ES
dc.subjectPHASE-2 TRIALes_ES
dc.subjectIN-VIVOes_ES
dc.subjectPOLYPLOIDIZATIONes_ES
dc.subjectMITOSISes_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCell Cycle Proteins es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshFlow Cytometry es_ES
dc.subject.meshFluorescent Antibody Technique es_ES
dc.subject.meshM Phase Cell Cycle Checkpoints es_ES
dc.subject.meshMegakaryocytes es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshProtein-Serine-Threonine Kinases es_ES
dc.subject.meshProto-Oncogene Proteins es_ES
dc.subject.meshThrombocytopenia es_ES
dc.titleActivation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID26185128es_ES
dc.format.volume126es_ES
dc.format.number14es_ES
dc.format.page1707-14es_ES
dc.identifier.doi10.1182/blood-2015-03-634402es_ES
dc.contributor.funderFundación La Caixa 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderWorldwide Cancer Research 
dc.contributor.funderUnión Europea 
dc.contributor.funderConsolider-Ingenio Programme
dc.description.peerreviewedes_ES
dc.identifier.e-issn1528-0020es_ES
dc.relation.publisherversionhttps://doi.org/10.1182/blood-2015-03-634402es_ES
dc.identifier.journalBloodes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de División Celular y Cánceres_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2012-38215es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BFU2014-52125-REDTes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ S2010/BMD-2470es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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