Caspases play an essential role in the execution of programmed cell death i
n metazoans, Although 14 caspases are known in mammals, only a few have bee
n described in other organisms. Here we describe the identification and cha
racterization of a Drosophila caspase, DRONC, that contains an amino termin
al caspase recruitment domain. Ectopic expression of DRONC in cultured cell
s resulted in apoptosis, which was inhibited by the caspase inhibitors p35
and MIHA, DRONC exhibited a substrate specificity similar to mammalian casp
ase-2, DRONC is ubiquitously expressed in Drosophila embryos during early s
tages of development. In late third instar larvae, drone mRNA is dramatical
ly upregulated in salivary glands and midgut before histolysis of these tis
sues. Exposure of salivary glands and midgut isolated from second instar la
rvae to ecdysone resulted in a massive increase in drone mRNA levels. These
results suggest that DRONC is an effector of steroid-mediated apoptosis du
ring insect metamorphosis.