IDENTIFICATION OF A DROSOPHILA-MELANOGASTER ICE CED3-RELATED PROTEASE, DRICE/

Cysteine proteases of the ICE/CED3 family (caspases) are required for the execution of programmed cell death (PCD) in a wide range of multic ellular organisms. Caspases are implicated in the execution of apoptos is in Drosophila melanogaster by the observation that expression of ba culovirus p35, a caspase inhibitor, blocks cell death irt vivo in Dros ophila, We report here the identification and characterization of drIC E, a D. melanogaster caspase. We show that overexpression of drICE sen sitizes Drosophila cells to apoptotic stimuli and that expression of a n N-terminally truncated form of drICE rapidly induces apoptosis in Dr osophila cells, Induction of apoptosis by rpr overexpression or by cyc loheximide or etoposide treatment of Drosophila cells results in prote olytic processing of drICE. We further show that drICE is a cysteine p rotease that cleaves baculovirus p35 and Drosophila Iamin DmO in vitro and that drICE is expressed at all the stages of Drosophila developme nt at which PCD can be induced, Taken together, these results strongly argue that drICE is an apoptotic caspase that acts downstream of rpr. drICE is therefore the first unequivocal link between the molecular m achinery of Drosophila cell death and the conserved machinery of Caeno rhabditis elegans and vertebrates, Identification of drICE should faci litate the elucidation of upstream regulators and downstream targets o f caspases by genetic screening.