The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila.
Caspases are essential components of the apoptotic machinery in both vertebrates and invertebrates. Here, we report the isolation of a mutant allele of the Drosophila effector caspase drICE as a strong suppressor of hid- (head involution defective-) induced apoptosis. This mutant was used to determine the apoptotic role of drICE. Our data are consistent with an important function of drICE for developmental and irradiation-induced cell death. Epistatic analysis suggests that drICE acts genetically downstream of Drosophila inhibitor of apoptosis protein 1 (Diap1). However, although cell death is significantly reduced in drICE mutants in all assays, it is not completely blocked. A double-mutant analysis between drICE and death caspase-1 (dcp-1), another effector caspase, reveals that some cells (type I) strictly require drICE for apoptosis, whereas other cells (type II) require either drICE or dcp-1. Thus, these data demonstrate a barely appreciated complexity in the apoptotic pathway, and are consistent with current models about effector caspase regulation in both vertebrates and invertebrates.
Xu
D
D
Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1000, Houston, TX 77030, USA.
Wang
Y
Y
Willecke
R
R
Chen
Z
Z
Ding
T
T
Bergmann
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic; D005123:Eye / Q000254:growth & development; D017344:Genes, Insect; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D020169:Caspases; C103568:Dcp-1 protein, Drosophila; C109171:drICE protein, Drosophila