protein is required for DNA damage-induced cell death (Brodsky et al., 2000;
Ollmann et al., 2000). A radiation-responsive element in the Rpr promoter contains
a p53-binding site. This strongly suggests that ionizing radiation activates apoptosis
in flies by inducing Rpr expression in a p53-dependent manner. Characterization of
p53-induced death in a Rpr mutant, as described below, indicates that there are other
p53 targets (Peterson et al., 2002).
Hid is more broadly expressed than Rpr, Grim, and Skl. Although Hid is a potent
inducer of cell death when ectopically expressed, Hid mRNA is observed in cells that
do not undergo apoptosis (Grether et al., 1995). This suggests that Hid activity can
be modulated post-transcriptionally. Hid has been shown to be activated when
growth factor signaling through the Ras/Raf/MAPK pathway is inhibited (Bergmann
et al., 1998; Kurada and White, 1998; Bergmann et al., 2002). MAPK activation
through this pathway inhibits Hid transcription, and also appears to inhibit Hid
function by direct phosphorylation of the protein.
8.
What is the role of apoptosis in Drosophila development?Apoptosis serves to remove excess and effete cells during development in Drosophila,
just as it does in other animals (Jacobson et al., 1997). Throughout development,
excess cells are generated, and then eliminated by apoptosis. The functions of Rpr,
Grim, and Hid are required for the majority of developmental apoptosis outside the
female germ line (Foley and Cooley, 1998). Examination of the phenotypes of
mutants that remove one or more of these genes allows the identification of cells that
are normally eliminated by apoptosis, and provides clues as to how these deaths are
regulated. Characterization of Hid and Rpr mutants has shown that these genes are
responsible for different subsets of developmental deaths.
Table 1. Signals that regulate apoptotic functions in Drosophila
194 GENETICS OF APOPTOSIS