IDENTIFICATION AND CHARACTERIZATION OF A NEW MEMBER OF THE TNF FAMILYTHAT INDUCES APOPTOSIS

A novel tumor necrosis factor (TNF) family member has been cloned and characterized. This protein, designated TNF-related apoptosis-inducing ligand (TRAIL), consists of 281 and 291 aa in the human and murine fo rms, respectively, which share 65% aa identity. TRAIL is a type II mem brane protein, whose C-terminal extracellular domain shows clear homol ogy to other TNF family members. TRAIL transcripts are detected in a v ariety of human tissues, most predominantly in spleen, lung, and prost ate. The TRAIL gene is located on chromosome 3 at position 3q26, which is not close to any other known TNF ligand family members. Both full- length cell surface expressed TRAIL and picomolar concentrations of so luble TRAIL rapidly induce apoptosis in a wide variety of transformed cell lines of diverse origin.