A screen for suppressors of apoptosis identifies a novel gain of function mutation in drosphilia RAS1s

Background: Apoptosis is a morphologically distinct, genetically programmed form of cell death that is evolutionarily highly conserved amongst multi-cellular eukaryotes. Correct regulation of apoptosis is critical for normal development and the prevention of diseases, such as cancer. Genetic analysis of invertebrate model organisms has proven invaluable for the identification and study of key molecules involved in apoptosis. In Drosophila, the proteins Reaper (Rpr), Head involution defective (Hid) and Grim induce cell death in a caspase dependent manner by inhibiting the anti-apoptotic function of diap1. Methods: To further elucidate the molecular mechanisms underlying the control of apoptosis, we conducted a dominant modifier screen for genes that could suppress the strong eye ablation phenotype caused by expressing hid under the control of an eye-specific promoter. Results: As previously reported, we identified several loss of function mutants in components of the EGFR/Ras/MAPK pathway that could dominantly suppress hid-induced apoptosis. These mutants proved to be alleles of either sprouty or gap1, two negative regulators of the RTK/Ras1 signaling. Here we report the identification and characterization of the first gain of function mutation in the Drosophila RAS1 gene. Conclusions: Taken together, these findings provide a molecular paradigm for the anti-apoptotic function of ras oncogenes.