Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies

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 inmice leads to a non-mitotic arr...

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Detalles Bibliográficos
Autores: Wachowicz, Paulina, Fernandez-Miranda, Gonzalo, Marugan, Carlos, Escobar, Beatriz, de Carcer, Guillermo
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/5212
Acceso en línea:http://hdl.handle.net/20.500.12105/5212
Access Level:acceso abierto
Palabra clave:cell cycle
development
mitosis
Polo-like kinase 1
spindle dynamics
CELL-CYCLE
PROTEIN-KINASE
BOX DOMAIN
SACCHAROMYCES-CEREVISIAE
CHROMOSOME SEGREGATION
MAMMALIAN-CELLS
DROSOPHILA POLO
CENTROSOMAL LOCALIZATION
TUMOR SUPPRESSION
CANCER-THERAPY
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/5212
network_acronym_str ES
network_name_str España
repository_id_str
spelling Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberranciesWachowicz, PaulinaFernandez-Miranda, GonzaloMarugan, CarlosEscobar, Beatrizde Carcer, Guillermocell cycledevelopmentmitosisPolo-like kinase 1spindle dynamicsCELL-CYCLEPROTEIN-KINASEBOX DOMAINSACCHAROMYCES-CEREVISIAECHROMOSOME SEGREGATIONMAMMALIAN-CELLSDROSOPHILA POLOCENTROSOMAL LOCALIZATIONTUMOR SUPPRESSIONCANCER-THERAPYPolo-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 inmice 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.WileyEuropean CommissionComunidad de Madrid20172017-10-3020162016-01-0120162016-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/5212reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/52122026-06-12T12:43:37Z
dc.title.none.fl_str_mv Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
title Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
spellingShingle Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
Wachowicz, Paulina
cell cycle
development
mitosis
Polo-like kinase 1
spindle dynamics
CELL-CYCLE
PROTEIN-KINASE
BOX DOMAIN
SACCHAROMYCES-CEREVISIAE
CHROMOSOME SEGREGATION
MAMMALIAN-CELLS
DROSOPHILA POLO
CENTROSOMAL LOCALIZATION
TUMOR SUPPRESSION
CANCER-THERAPY
title_short Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
title_full Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
title_fullStr Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
title_full_unstemmed Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
title_sort Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies
dc.creator.none.fl_str_mv Wachowicz, Paulina
Fernandez-Miranda, Gonzalo
Marugan, Carlos
Escobar, Beatriz
de Carcer, Guillermo
author Wachowicz, Paulina
author_facet Wachowicz, Paulina
Fernandez-Miranda, Gonzalo
Marugan, Carlos
Escobar, Beatriz
de Carcer, Guillermo
author_role author
author2 Fernandez-Miranda, Gonzalo
Marugan, Carlos
Escobar, Beatriz
de Carcer, Guillermo
author2_role author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Comunidad de Madrid
dc.subject.none.fl_str_mv cell cycle
development
mitosis
Polo-like kinase 1
spindle dynamics
CELL-CYCLE
PROTEIN-KINASE
BOX DOMAIN
SACCHAROMYCES-CEREVISIAE
CHROMOSOME SEGREGATION
MAMMALIAN-CELLS
DROSOPHILA POLO
CENTROSOMAL LOCALIZATION
TUMOR SUPPRESSION
CANCER-THERAPY
topic cell cycle
development
mitosis
Polo-like kinase 1
spindle dynamics
CELL-CYCLE
PROTEIN-KINASE
BOX DOMAIN
SACCHAROMYCES-CEREVISIAE
CHROMOSOME SEGREGATION
MAMMALIAN-CELLS
DROSOPHILA POLO
CENTROSOMAL LOCALIZATION
TUMOR SUPPRESSION
CANCER-THERAPY
description 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 inmice 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01
2016
2016-01-01
2017
2017-10-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/5212
url http://hdl.handle.net/20.500.12105/5212
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406305442070528
score 15,812429

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