title: The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle.
abstract: Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centriole duplication occurs once per cell cycle and is controlled by Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradation by the proteasome. Here we demonstrate that this autoregulated instability controls the abundance of endogenous Plk4. Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation; moreover, suppression of p53 allows growth of cells carrying amplified centrosomes. Plk4 autoregulation thus guards against genome instability by limiting centrosome duplication to once per cell cycle.
authors.affiliation: Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA. a1holland@ucsd.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holland
authors.forename: Daniele
authors.initials: D
authors.lastname: Fachinetti
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Manuel
authors.initials: M
authors.lastname: Bauer
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D018385:Centrosome / Q000502:physiology*; D004795:Enzyme Stability / Q000502:physiology; D018390:Gene Targeting; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases