Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its rec eptors are members of the tumor necrosis factor superfamily. TRAIL selectiv ely kills cancer cells but not normal cells. We report here the cloning of the mouse homologue of the TRAIL receptor KILLER/DR5 (MK). The cDNA of MK i s 1146 bp in length and encodes a protein of 381 amino acids. MK contains a n extracellular cysteine-rich domain, a transmembrane domain, and a cytopla smic death-domain characteristic of Fas, tumor necrosis factor, and human T RAIL receptors, MK is highly homologous and binds TRAIL with similar affini ty as human DR4 and KILLER/DR5, MK induces apoptosis in mouse and human cel ls and inhibits colony growth of NIH3T3 cells. Expression of MK is p53-depe ndent and up-regulated by tumor suppressor p53 and by DNA damaging agents i n mouse cells undergoing apoptosis, This is the first report describing a m ouse TRAIL receptor gene and also demonstrating that the p53-dependent regu lation of KILLER/DR5-mediated apoptosis is conserved between human and mous e.