title: Drosophila p53 binds a damage response element at the reaper locus.
abstract: The tumor suppressor gene p53 regulates multiple cellular responses to DNA damage, but the transcriptional targets that specify these responses are incompletely understood. We describe a Drosophila p53 homolog and demonstrate that it can activate transcription from a promoter containing binding sites for human p53. Dominant-negative forms of Drosophila p53 inhibit both transactivation in cultured cells and radiation-induced apoptosis in developing tissues. The cis-regulatory region of the proapoptotic gene reaper contains a radiation-inducible enhancer that includes a consensus p53 binding site. Drosophila p53 can activate transcription from this site in yeast and a multimer of this site is sufficient for radiation induction in vivo. These results indicate that reaper is a direct transcriptional target of Drosophila p53 following DNA damage.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Brodsky
authors.forename: W
authors.initials: W
authors.lastname: Nordstrom
authors.forename: G
authors.initials: G
authors.lastname: Tsang
authors.forename: E
authors.initials: E
authors.lastname: Kwan
authors.forename: G M
authors.initials: GM
authors.lastname: Rubin
authors.forename: J M
authors.initials: JM
authors.lastname: Abrams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D018076:DNA, Complementary; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004742:Enhancer Elements, Genetic; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; D019476:Insect Proteins; D010455:Peptides; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C086973:rpr protein, Drosophila; D004247:DNA