Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator.
We identified a Drosophila Apaf-1/CED-4 homolog gene, dapaf-1. Alternative splicing results in two dapaf-1 mRNA species, which encode distinct forms of caspase activator, Dapaf-1L (Apaf-1 type) and Dapaf-1S (CED-4 type). Distinct caspases were activated by these Dapaf-1 isoforms. Loss of Dapaf-1 function resulted in defective cytochrome c-dependent caspase activities and reduced apoptosis in embryo and in larval brain. Dapaf-1 activities were also involved in cell death induced by ectopic expression of reaper in the compound eye. These data suggest that Dapaf-1/cytochrome c-dependent cell death-inducing machinery is present in Drosophila, and the requirement of Dapaf-1/Apaf-1 in neural cell death is conserved through evolution.
Kanuka
H
H
Department of Neuroscience, Osaka University Graduate School of Medicine, Japan.
Sawamoto
K
K
Inohara
N
N
Matsuno
K
K
Okano
H
H
Miura
M
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003574:Cytochrome c Group / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D019143:Evolution, Molecular; D005123:Eye / Q000166:cytology / Q000378:metabolism; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D003574:Cytochrome c Group; D029721:Drosophila Proteins; D015801:Helminth Proteins; D010455:Peptides; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; C086973:rpr protein, Drosophila; D020169:Caspases