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Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila

Malte Peters1, Carmela DeLuca, Atsushi Hirao

  • 1Advanced Medical Discoveries Institute, Ontario Cancer Institute, University of Toronto, 620 University Avenue, Toronto, ON, Canada M5G 2C1.

Proceedings of the National Academy of Sciences of the United States of America
|August 13, 2002
PubMed

Insights

In Drosophila, the tumor suppressor p53

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • The tumor suppressor p53 regulates apoptosis and cell cycle.
  • Mammalian p53 is activated by DNA damage and other stresses via posttranslational modifications.
  • Regulation of p53 in Drosophila melanogaster remains largely unknown.

Purpose of the Study:

  • Investigate the regulation of Drosophila p53 (Dmp53).
  • Determine the role of Chk2 and Chk1 homologs in Dmp53 function.

Main Methods:

  • Overexpression of Dmp53 in Drosophila eyes.
  • Coexpression with Drosophila Chk2 (DmChk2) and Chk1 (Grapes).
  • Use of dominant-negative (DN) mutants.
  • Site-directed mutagenesis of Dmp53.

Main Results:

  • Dmp53 overexpression induces apoptosis and a small eye phenotype.
  • DmChk2 enhances Dmp53-induced apoptosis and transactivation.
  • A specific serine residue (Ser-4) on Dmp53 is critical for DmChk2-mediated activation.
  • Drosophila Chk1 (Grapes) does not affect Dmp53 phenotypes.

Conclusions:

  • DmChk2 activates the apoptotic function of Dmp53.
  • Ser-4 phosphorylation is essential for DmChk2-Dmp53 interaction.
  • DmChk2, not Chk1, is involved in regulating Dmp53 in Drosophila.
  • Chk2 may be an ancestral regulator of p53.

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