INTERACTION AND REGULATION OF SUBCELLULAR-LOCALIZATION OF CED-4 BY CED-9

The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activit y and inhibits is cell death, but the mechanism by which this occurs i s unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss -of-function mutants, associated specifically with CED-4 in yeast or m ammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 Was distributed i n the cytosol. Expression of CED-9, but not a mutant lacking the carbo xy-terminal hydrophobic domain, targeted CED-4 from the cytosol to int racellular membranes in mammalian cells. Thus, the actions of CED-4 an d CED-9 are directly linked, which could provide the basis for the reg ulation of programmed cell death in C. elegans.