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dc.contributor.author | Trakala, Marianna | |
dc.contributor.author | Partida, David | |
dc.contributor.author | Salazar-Roa, Maria | |
dc.contributor.author | Maroto, María | |
dc.contributor.author | Wachowicz, Paulina | |
dc.contributor.author | de Carcer Diez, Guillermo | |
dc.contributor.author | Malumbres Martinez, Marcos | |
dc.date.accessioned | 2020-06-23T16:30:53Z | |
dc.date.available | 2020-06-23T16:30:53Z | |
dc.date.issued | 2015-10-01 | |
dc.identifier.citation | Blood . 2015;126(14):1707-14. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10543 | |
dc.description.abstract | Polyploidization 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | American Society of Hematology (ASH) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | POLO-LIKE KINASES | es_ES |
dc.subject | VOLASERTIB BI 6727 | es_ES |
dc.subject | CELL-CYCLE | es_ES |
dc.subject | AURORA-B | es_ES |
dc.subject | MEGAKARYOCYTE ENDOMITOSIS | es_ES |
dc.subject | INHIBITOR VOLASERTIB | es_ES |
dc.subject | PHASE-2 TRIAL | es_ES |
dc.subject | IN-VIVO | es_ES |
dc.subject | POLYPLOIDIZATION | es_ES |
dc.subject | MITOSIS | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Cycle Proteins | es_ES |
dc.subject.mesh | Cell Differentiation | es_ES |
dc.subject.mesh | Flow Cytometry | es_ES |
dc.subject.mesh | Fluorescent Antibody Technique | es_ES |
dc.subject.mesh | M Phase Cell Cycle Checkpoints | es_ES |
dc.subject.mesh | Megakaryocytes | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Protein-Serine-Threonine Kinases | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins | es_ES |
dc.subject.mesh | Thrombocytopenia | es_ES |
dc.title | Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 26185128 | es_ES |
dc.format.volume | 126 | es_ES |
dc.format.number | 14 | es_ES |
dc.format.page | 1707-14 | es_ES |
dc.identifier.doi | 10.1182/blood-2015-03-634402 | es_ES |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Worldwide Cancer Research | |
dc.contributor.funder | Unión Europea | |
dc.contributor.funder | Consolider-Ingenio Programme | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1528-0020 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1182/blood-2015-03-634402 | es_ES |
dc.identifier.journal | Blood | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de División Celular y Cáncer | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2012-38215 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2014-57791-REDC | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/BFU2014-52125-REDT | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ S2010/BMD-2470 | es_ES |
dc.rights.accessRights | open access | es_ES |