title: Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies.
abstract: Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays multiple and essential roles during the cell division cycle. Its inhibition in cultured cells leads to severe mitotic aberrancies and cell death. Whereas previous reports suggested that Plk1 depletion in mice leads to a non-mitotic arrest in early embryos, we show here that the bi-allelic Plk1 depletion in mice certainly results in embryonic lethality due to extensive mitotic aberrations at the morula stage, including multi- and mono-polar spindles, impaired chromosome segregation and cytokinesis failure. In addition, the conditional depletion of Plk1 during mid-gestation leads also to severe mitotic aberrancies. Our data also confirms that Plk1 is completely dispensable for mitotic entry in vivo. On the other hand, Plk1 haploinsufficient mice are viable, and Plk1-heterozygous fibroblasts do not harbor any cell cycle alterations. Plk1 is overexpressed in many human tumors, suggesting a therapeutic benefit of inhibiting Plk1, and specific small-molecule inhibitors for this kinase are now being evaluated in clinical trials. Therefore, the different Plk1 mouse models here presented are a valuable tool to reexamine the relevance of the mitotic kinase Plk1 during mammalian development and animal physiology.
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Ecole polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Wachowicz
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Institute for Research in Biomedicine (IRB), Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Fernández-Miranda
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Marugán
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Spanish National Cardiovascular Research Centre (CNIC), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Escobar
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Cárcer
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D020090:Chromosome Segregation; D048749:Cytokinesis; D005260:Female; D008297:Male; D051379:Mice; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000502:physiology; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
keywords: Polo-like kinase 1; cell cycle; development; mitosis; spindle dynamics