Genotoxic stress-induced activation of Plk3 is partly mediated by Chk2.
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.
Xie
Suqing
S
Division of Molecular Carcinogenesis, Brander Cancer Institute, Department of Medicine, Valhalla, New York, USA.
Wu
Huiyun
H
Wang
Qi
Q
Kunicki
Jan
J
Thomas
Raymond O
RO
Hollingsworth
Robert E
RE
Cogswell
John
J
Dai
Wei
W
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000097868:Polo-like Kinases
D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C578634:CHEK2 protein, human