Identification and characterization of a p53 homologue in Drosophila melanogaster

The tumor suppressor gene p53 in mammalian cells plays a critical role in s afeguarding the integrity of genome. It functions as a sequence-specific tr anscription factor. Upon activation by a variety of cellular stresses, p53 transactivates downstream target genes, through which it regulates cell cyc le and apoptosis. However, little is known about p53 in invertebrates. Here we report the identification and characterization of a Drosophila p53 homo logue gene. dp53. dp53 encodes a 385-amino acid protein with significant ho mology to human p53 (hp53) in the region of the DNA-binding domain, and to a lesser extent the tetramerization domain. Purified dp53 DNA-binding domai n protein was shown to bind to the consensus hp53-binding site by gel mobil ity analysis. In transient transfection assays, expression of dp53 in Schne ider cells transcriptionally activated promoters that contained consensus h p53-responsive elements. Moreover, a mutant dp53 (Arg-155 to His-155), like its hp53 counterpart mutant, exerted a dominant-negative effect on transac tivation. Ectopic expression of dp53 in Drosophila eye disk caused cell dea th and led to a rough eye phenotype. dp53 is expressed throughout the devel opment of Drosophila with highest expression levels in early embryogenesis, which has a maternal component. Consistent with this, dp53 RNA levels were high in the nurse cells of the ovary. It appears that p53 is structurally and functionally conserved from flies to mammals. Drosophila will provide a useful genetic system to the further study of the p53 network.