The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle

Andrew J. Holland, Daniele Fachinetti, Quan Zhu, Manuel Bauer, Inder M. Verma, Erich A. Nigg, Don W. Cleveland

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2684-2689
Number of pages6
JournalGenes and Development
Volume26
Issue number24
DOIs
StatePublished - 2012

Keywords

  • Aneuploidy
  • Centriole
  • Centrosome
  • Genome instability
  • Mitosis
  • P53
  • SCF

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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