Multicellular organisms have a mechanism to eliminate unnecessary or harmful cells during development and tissue maintenance. Recent studies suggest that this process of programmed cell death is molecularly conserved throughout the animal kingdom. We are analyzing a new cell death inhibitor,
dad-1, that functions in both C. elegans and vertebrates. The
dad-1 gene, which encodes a novel protein, was originally identified in a mutant hamster cell line (tsBN7) that undergoes apoptosis at restrictive temperature. We identified a
dad-1 homologue in C. elegans whose predicted product is >60% identical to vertebrate DAD-1. From the sequence databases, we also identified cDNA sequences encoding
dad-1-like proteins from two plant species, Arabidopsis thaliana and the rice Oryza sativa. To test whether
dad-1 is sufficient to prevent cell death, we generated worms transgenic for
dad-1 genes expressed under control of a heat-shock promoter. Heat-shock-induced expression of either human or C. elegans
dad-1 reduced the number of cell corpses present at comma stage. Extra cells were observed in the anterior pharynx of heat-shocked animals, confirming that cell deaths were indeed prevented. The C. elegans
dad-1 gene was found to rescue mutant tsBN7 hamster cells from apoptotic death as efficiently as vertebrate
dad-1 genes. Thus,
dad-1 is a functionally conserved cell death suppressor that appears to be necessary (in cultured hamster cells) and sufficient (in C. elegans) to promote cell survival. In attempt to isolate loss-of-function mutants of
Ce-dad-1, we have isolated multiple Tc1 insertions in the gene and are characterizing the expression pattern of the gene.