Reaper-induced apoptosis in a vertebrate system.
The reaper protein of Drosophila melanogaster has been shown to be a central regulator of apoptosis in that organism. However, it has not been shown to function in any vertebrate nor have the cellular components required for its action been defined. In this report we show that reaper can induce rapid apoptosis in vitro using an apoptotic reconstitution system derived from Xenopus eggs. Moreover, we show that a subcellular fraction enriched in mitochondria is required for this process and that reaper, acting in conjunction with cytosolic factors, can trigger mitochondrial cytochrome c release. Bcl-2 antagonizes these effects, but high levels of reaper can overcome the Bcl-2 block. These results demonstrate that reaper can function in a vertebrate context, suggesting that reaper-responsive factors are conserved elements of the apoptotic program.
Evans
E K
EK
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3686, C366 LSRC, Research Drive, Durham, NC 27710, USA.
Kuwana
T
T
Strum
S L
SL
Smith
J J
JJ
Newmeyer
D D
DD
Kornbluth
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005260:Female; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D010455:Peptides / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014714:Vertebrates; D014981:Xenopus
D003574:Cytochrome c Group; D029721:Drosophila Proteins; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; C086973:rpr protein, Drosophila; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1