In contrast to growth factors which promote cell proliferation, FAS ligand (FAS-L) and the tumor necrosis factors (TNFs) rapidly induce apoptosis. Cellular response to FAS-L and TNF is mediated by structurally related receptors containing a conserved cytoplasmic region called the “death domain”. DAP-1 (for death associated protein-1) interacts with the death domain of TNF-R1 and can trigger programmed cell death in a variety of cell lines, as well as suppress NFκB/Rel activity. DAP-3 is a positive mediator of programmed cell death; overexpressed intact full-length protein is required in order to induce apoptosis. During apotosis, the caspase-activated DAP-5 can mediate CAP-independent translation at least from its own internal ribosome entry site, thus resulting in a positive feedback loop responsible for the continuous translation of DAP-5. DAP-5 is also required for cellular differentiation, as it controls specific gene expression pathways.
