title: Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim.
abstract: In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (DeltaN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (DeltaN-drICE) in the retina showed no obvious eye phenotype. Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-DeltaN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo.
authors.affiliation: Departments of Biology and Brain and Cognitive Sciences, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: B
authors.initials: B
authors.lastname: Guan
authors.forename: A
authors.initials: A
authors.lastname: Bergman
authors.forename: D W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: N A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: E P
authors.initials: EP
authors.lastname: Peterson
authors.forename: H
authors.initials: H
authors.lastname: Steller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D006801:Humans; D009479:Neuropeptides / Q000235:genetics*; D010455:Peptides / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D009479:Neuropeptides; D010455:Peptides; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D020169:Caspases