activity of a limited number of transcription factors, which in turn integrate several
signaling pathways. Furthermore, it is not known whether these genes share regulatory
sequences. Although the genes are clustered on the chromosome, they are spread over
more than 100 kb (Adams et al., 2000). Detailed molecular studies will reveal whether
this region contains regulatory sequences that are shared by more than one gene.
Although the developmental pathways that regulate Rpr expression during
embryogenesis have not yet been described, two regulators have been identified that
directly activate the Rpr promoter: the steroid hormone receptor and p53. Expression
of Rpr is detected in many effete larval tissues, shortly before they undergo apoptosis.
The death of these tissues depends on changes in the level of the steroid hormone
ecdysone. The Rpr promoter contains a steroid hormone-binding site, which is
sufficient to activate Rpr expression in response to ecdysone (Jiang et al., 2000).
Expression of Hid, Dronc, and Damm is also activated in response to steroid
hormones, although the activation of Hid is likely to be indirect. It is interesting to
note that Rpr expression is turned on in some cells by rising titers of ecdysone, and
in some tissues by falling titers (Robinow et al., 1997). Apoptosis is also limited to a
subset of tissues that respond to the hormone (Robinow et al., 1993).
Exposure to ionizing radiation induces the expression of Rpr and SkI, and
subsequent apoptosis (Nordstrom et al., 1996; Brodsky et al., 2000; Christich et al.,
2002). Studies using a dominant negative form of Drosophila p53 indicate that this
Figure 1. A speculative model for the interactions between proteins involved in apoptosis in
Drosophila.
The interactions between the apoptotic inducers Rpr, Grim, Hid, and SkI and DIAP1, and
between DIAP1 and some of the caspases are supported by experimental data (see text).
However, the mechanisms by which these inducers activate the mitochondria pathway are
unknown. Genes shown to be involved in apoptosis in vivo are in bold. Speculative interactions
are indicated by dotted lines.
APOPTOSIS IN DROSOPHILA 193