Genotoxic stress-induced activation of Plk3 is partly mediated by Chk2

Cell Cycle. Nov-Dec 2002;1(6):424-9. doi: 10.4161/cc.1.6.271.

Abstract

Polo-like kinase 3 (Plk3, alternatively termed Prk) is involved in the regulation of DNA damage checkpoint as well as in M-phase function. Plk3 physically interacts with p53 and phosphorylates this tumor suppressor protein on serine-20, suggesting that the role of Plk3 in cell cycle progression is mediated, at least in part, through direct regulation of p53. Here we show that Plk3 is rapidly activated by reactive oxygen species in normal diploid fibroblast cells (WI-38), correlating with a subsequent increase in p53 protein level. Plk3 physically interacts with Chk2 and the interaction is enhanced upon DNA damage. In addition, Chk2 immunoprecipitated from cell lysates of Daudi (which expressed little Plk3) is capable of stimulating the kinase activity of purified recombinant Plk3 in vitro, and this stimulation is more pronounced when Plk3 is supplemented with Chk2 immunoprecipitated from Daudi after DNA damage. Furthermore, ectopic expression Chk2 activates cellular Plk3. Together, our studies suggest Chk2 may mediate direct activation of Plk3 in response to genotoxic stresses.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Checkpoint Kinase 2
  • DNA Damage / drug effects
  • DNA Damage / genetics*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Reactive Oxygen Species / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Cell Cycle Proteins
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Protein Kinases
  • PLK3 protein, human
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases