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Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis

dc.contributor.authorHolland, A. J.
dc.contributor.authorFachinetti, D.
dc.contributor.authorDa Cruz, S.
dc.contributor.authorZhu, Q.
dc.contributor.authorVitre, B.
dc.contributor.authorLince-Faria, M.
dc.contributor.authorChen, D.
dc.contributor.authorParish, N.
dc.contributor.authorVerma, I. M.
dc.contributor.authorBettencourt-Dias, M.
dc.contributor.authorCleveland, D. W.
dc.date.accessioned2016-06-09T11:39:19Z
dc.date.available2016-06-09T11:39:19Z
dc.date.issued2012-03-20
dc.description.abstractCentrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis.pt_PT
dc.description.sponsorshipNational Institutes of Health grant: (GM29513); Ludwig Institute for Cancer Research; Leukemia and Lymphoma Society Special Fellowship; European Molecular Biology Organization (EMBO) long-term fellowship; Human Frontier Science Program (HFSP) postdoctoral fellowship.pt_PT
dc.identifier.citationAndrew J. Holland, Daniele Fachinetti, Sandrine Da Cruz, Quan Zhu, Benjamin Vitre, Mariana Lince-Faria, Denaly Chen, Nicole Parish, Inder M. Verma, Monica Bettencourt-Dias, and Don W. Cleveland Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis Mol. Biol. Cell 2012 23:10 1838-1845; First Published on March 28, 2012; doi:10.1091/mbc.E11-12-1043pt_PT
dc.identifier.doi10.1091/mbc.E11-12-1043pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/634
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherThe American Society for Cell Biologypt_PT
dc.relation.publisherversionhttp://www.molbiolcell.org/content/23/10/1838.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.subjectAnimalspt_PT
dc.subjectCell Linept_PT
dc.subjectCentriolespt_PT
dc.subjectCentrosomept_PT
dc.subjectFibroblastspt_PT
dc.subjectGene Knockdown Techniquespt_PT
dc.subjectHeterozygotept_PT
dc.subjectHumanspt_PT
dc.subjectMicept_PT
dc.subjectMicrotubulespt_PT
dc.subjectPhenotypept_PT
dc.subjectProtein Transportpt_PT
dc.subjectProtein-Serine-Threonine Kinasespt_PT
dc.subjectRNA Interferencept_PT
dc.subjectSpindle Apparatuspt_PT
dc.subjectTime-Lapse Imagingpt_PT
dc.subjectCytokinesispt_PT
dc.titlePolo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1845pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage1838pt_PT
oaire.citation.titleMolecular Biology of the Cellpt_PT
oaire.citation.volume23pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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