title: Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop.
abstract: 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.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Riddhita
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Kent G
authors.initials: KG
authors.lastname: Golic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D025461:Feedback, Physiological / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000607164:CorP protein, Drosophila; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; D051736:Proto-Oncogene Proteins c-mdm2