GRIM, A NOVEL CELL-DEATH GENE IN DROSOPHILA

A genomic interval at 75C1,2 is required for programmed cell death in Drosophila. We identified a new activator of apoptosis, grim, which ma ps between two previously identified cell death genes in this region r eaper (rpr) and head involution defective (hid). Expression of grim RN A coincided with the onset of programmed cell death at all stages of e mbryonic development, whereas ectopic induction of grim triggered exte nsive apoptosis in both transgenic animals and in cell culture. Cell k illing by grim was blocked by coexpression of p35, a viral product tha t inactivates ICE-like proteases, and did not require the functions of rpr or hid. The predicted grim protein shares an amino-terminal motif in common with rpr. However, grim was sufficient to elicit apoptosis in at least one context, where rpr was not. The grim gene product migh t thus function in a parallel circuit of cell death signaling that ult imately activates a common set of downstream apoptotic effecters.