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Reaper-induced apoptosis in a vertebrate system
E K Evans1, T Kuwana, S L Strum
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3686, C366 LSRC, Research Drive, Durham, NC 27710, USA.
The EMBO Journal
|February 21, 1998
Summary
The reaper protein triggers apoptosis in vertebrates, utilizing mitochondria and cytosolic factors. This suggests conserved components of the cell death pathway across species.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- The reaper protein regulates apoptosis in Drosophila.
- Reaper's function and required components in vertebrates remain undefined.
Purpose of the Study:
- To investigate reaper's apoptotic function in a vertebrate system.
- To identify cellular components necessary for reaper-induced apoptosis.
Main Methods:
- In vitro apoptotic reconstitution system using Xenopus egg extracts.
- Mitochondrial enrichment and analysis of cytochrome c release.
- Investigation of Bcl-2 antagonism.
Main Results:
- Reaper induces rapid apoptosis in vitro.
- A mitochondrial fraction and cytosolic factors are essential for reaper's action.
- Reaper triggers mitochondrial cytochrome c release.
- Bcl-2 can antagonize reaper-induced apoptosis, but high reaper levels overcome this inhibition.
Conclusions:
- Reaper can function in a vertebrate context.
- Cellular factors mediating reaper's apoptotic activity are conserved.
- Mitochondria play a crucial role in reaper-mediated cell death.