Reaper Induced Cytochrome C Release
Annual summary rept. 1 Aug 2001-31 Jul 2002
DUKE UNIV MEDICAL CENTER DURHAM NC
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Apoptosis, or programmed cell death, is an energy-dependent process of cell suicide shown to be critical in many physiological and pathologic venues including tumor development. The gene reaper from Drosophila melanogaster, has proven roles in radiation-induced and developmental apoptosis, and is p53-induced. Using a cell-free extract system, our lab has identified a 150 kDa protein from Xenopus laevis called scythe that is required for reaper-induced apoptosis. The interaction of reaper with scythe liberates a soluble factor SCF that induces apoptosis by effecting the release of cytochrome c from mitochondria, a critical step in activating apoptosis in many systems. Our purpose is to identify and characterize SCF, and to evaluate its therapeutic potential. We have preliminary evidence that SCF at least in part contains the molecular chaperone Hsp70. Upon interaction with reaper, scythe releases Hsp70 which then acts at the mitochondrial surface to effect the redistribution of cytochrome c. As expected, blocking the chaperone activity of Hsp70 prevents reaper-induced apoptosis. We have successfully reconstituted this process in vitro using purified components. The next step in our research will be to identify the mitochondrial substrates of Hsp70 necessary for reaper-induced apoptosis.
- Medicine and Medical Research