Figure 2.

Programmed cell death pathways in Drosophila. In Drosophila, all embryonic PCD requires the activities of three closely linked genes, Rpr, Grim, and Hid. Expression of these apoptosis regulators initiates multiple downstream pathways to activate caspases and kill cells. Rpr, Grim, and Hid may induce formation of an apoptosome complex consisting of cytochrome c (cyt. c), Dark (Kanuka et al. 1999; Rodriguez et al. 1999; Zhou et al. 1999), and apical caspases such as Dronc (Loretta et al. 1999) and Dredd (Chen et al. 1998), which in turn promotes caspase activation and propagation of proteolytic activity to downstream, effector caspases (Abrams 1999). Alterations in cyt. c (Varkey et al. 1999) could be regulated by Scythe, a protein that binds all three death activators (Thress et al. 1999, Thress et al. 1998). Rpr, Grim, and Hid also engage caspases via one or more Dark-independent pathways. These involve derepression of native caspase inhibitors such as Diap1 (Wang et al. 1999). The pro-apoptotic Bcl-2 proteins (Drob-1/Debcl) probably function downstream of Rpr, Grim, and Hid and might directly engage caspases or function through Dark/cyt. c to propagate death signals. Currently, no pro-survival Bcl-2 gene has been reported in Drosophila.