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

Genes Dev. 2012 Dec 15;26(24):2684-9. doi: 10.1101/gad.207027.112.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Cycle / physiology*
  • Cell Division / genetics
  • Cell Line
  • Cell Proliferation
  • Centrosome / physiology*
  • Enzyme Stability / physiology
  • Gene Targeting
  • Homeostasis / physiology
  • Humans
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • PLK4 protein, human
  • Protein-Serine-Threonine Kinases