Annual summary rept. 1 Jul 1999-30 Jun 2003
DUKE UNIV MEDICAL CENTER DURHAM NC
Pagination or Media Count:
Reaper is a potent inducer of apoptotic cell death in the fruit fly Drosoophila melanogaster. Our lab unexpectedly discovered that Reaper also induces apoptosis in cultured human cells and cell free extracts prepared using eggs from the frog Xenopus laevis. In the Xenopus model system Reaper must bind another protein, Scythe, to induce apoptosis. Scythe forms a stable complex with the chaperone protein Hsp70 and inhibits its activity. Upon Reaper-Scythe binding, Hsp70 is released and free to refold protein substrates. Here we present evidence that the proapoptotic Bcl-2 family member BAX can be a target of the Reaper-Scythe-Hsp70 pathway. BAX is required for apoptosis mediated by mitochondrial cytochrome c release, and BAX is activated by regulated conformational change. BAX remains an attractive effector of the Reaper-Scythe proapoptotic pathway and further work will more completely characterize this novel mode of proapoptotic signaling.
- Medicine and Medical Research