Drosophila p53 binds a damage response element at the reaper locus.
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.
Brodsky
M H
MH
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
Nordstrom
W
W
Tsang
G
G
Kwan
E
E
Rubin
G M
GM
Abrams
J M
JM
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*
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