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The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes. This mechanism is evolutionarily conserved from mammals to lower invertebrates, including  Drosophila melanogaster . P53 also transcriptionally induces its primary negative regulator, Mdm2, which has not been found in  Drosophila . In this study we identified the  Drosophila  gene  companion of reaper  ( corp ) as a gene whose overexpression promotes survival of cells with DNA damage in the soma but reduces their survival in the germline. These disparate effects are shared by  p53  mutants, suggesting that Corp may be a negative regulator of P53. Confirming this supposition, we found that  corp  negatively regulates P53 protein level. It has been previously shown that P53 transcriptionally activates  corp ; thus, Corp produces a negative feedback loop on P53. We further found that  Drosophila  Corp shares a protein motif with vertebrate Mdm2 in a region that mediates the Mdm2:P53 physical interaction. In Corp, this motif mediates physical interaction with  Drosophila  P53. Our findings implicate Corp as a functional analog of vertebrate Mdm2 in flies.

Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop