THE RECEPTOR FOR THE CYTOTOXIC LIGAND TRAIL

TRAIL (also known as Apo-2L) is a member of the tumor necrosis factor (TNF) ligand family that rapidly induces apoptosis in a variety of tra nsformed cell lines. The human receptor for TRAIL was found to be an u ndescribed member of the TNF-receptor family (designated death recepto r-4, DR4) that contains a cytoplasmic ''death domain'' capable of enga ging the cell suicide apparatus but not the nuclear factor kappa B pat hway in the system studied. Unlike Fas, TNFR-1, and DR3, DR4 could not use FADD to transmit the death signal, suggesting the use of distinct proximal signaling machinery. Thus, the DR4-TRAIL axis defines anothe r receptor-ligand pair involved in regulating cell suicide and tissue homeostasis.