title: Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis.
abstract: Centrioles 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.
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holland
authors.forename: Daniele
authors.initials: D
authors.lastname: Fachinetti
authors.forename: Sandrine
authors.initials: S
authors.lastname: Da Cruz
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vitre
authors.forename: Mariana
authors.initials: M
authors.lastname: Lince-Faria
authors.forename: Denaly
authors.initials: D
authors.lastname: Chen
authors.forename: Nicole
authors.initials: N
authors.lastname: Parish
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: Monica
authors.initials: M
authors.lastname: Bettencourt-Dias
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000818:Animals; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D055785:Gene Knockdown Techniques; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases