Annual summary rept. 1 Jul 1999-30 Jun 2000
DUKE UNIV MEDICAL CENTER DURHAM NC
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Apoptosis is a program of cellular suicide which leads to the elimination of excess or damaged cells, while leaving neighboring cells unperturbed. Apoptosis is critical for organismal homeostasis in the adult and is an integral part of the developmental program in all metazoans. Genetic analysis in several organisms has successfully identified novel apoptotic regulators which, acting in conjunction with proteins such as IAPs, caspases, and Bcl-2 family members, are critical for implementation of the cell death program. In an extensive analysis of chromosomal deletion mutants in the fly, Drosophila Melanogaster, Steller and colleagues identified a chromosomal region containing a number of genes critical for programmed cell death occurring during embryonic. Three genes in this region encode, Reaper, Hid, and Grim proteins, which are potent cell death inducers. In their absence cell death is abrogated, while ectopic expression of these genes promotes apoptotic death not only in fly cells, but in human cells as well. We recently reported that Reaper-induced mitochondrial cytochrome c release and caspase activation in a cell-free extract of Xenopus eggs requires the presence of a 150 kD Reaper-binding protein, Scythe. We now show that Reaper binding to Scythe causes Scythe to release a sequestered apoptotic inducer. Upon release, the Scythe-sequestered factors is sufficient to induce cytochrome c release from purified mitochondria. Additionally, we have identified a region in Scythe which is homologous to a previously identified anti-apoptotic regulator, Bag-1.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research