Corp Regulates P53 in via a Negative Feedback Loop

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Organisms have exquisitely sensitive mechanisms to detect and respond to DNA damage. If DNA damage in a cell can be repaired, then that cell may resume its normal function. In multi-cellular organisms, if a cell cannot repair DNA damage it usually undergoes programmed cell death. This prevents the proliferation of cells with damaged genomes, which might otherwise differentiate incorrectly or proliferate without limit as cancer. In Drosophila melanogaster we identified corp as a gene that promotes the survival of such cells. Transcription of corp is activated by the P53 tumor suppressor protein, known primarily for its induction of cell death in response to DNA damage. Our experiments show that P53 regulates both pro-death and anti-death genes, and that a competition between these opposing factors determines cell fate. We find that corp functions by down-regulating P53, establishing a negative feedback loop. In vertebrates an identical mode of regulation is known: P53 up-regulates Mdm2, which physically interacts with P53 and is its primary negative regulator. We identified a protein motif on Corp that is shared with Mdm2, and is required for physical interaction between Corp and Drosophila P53. These results reinforce and strengthen the similarities of the P53 pathways and their regulation in vertebrates and in Drosophila.

Vyšlo v časopise: Corp Regulates P53 in via a Negative Feedback Loop. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005400
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005400

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