Apoptosis, or programmed cell death, occurs during normal cellular differentiation and development of multicellular organisms. Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors, TNFR1 and Fas. A novel member in the TNF family was recently identified and designated TRAIL (for TNF-related apoptosis-inducing ligand) and Apo-2L (for Apo-2 ligand) (1,2). TRAIL is a type II membrane protein and expressed in a variety of human tissues. Two novel death domain containing receptors DR4 and DR5 have been identified as the receptor for TRAIL (3-6). Like TNF and Fas ligand, TRAIL induces apoptosis and NF-kB activation in many tissues and cells.
1. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al. Identification and characterization of a new member of the TNF family that induces apoptosis.Immunity 3:673-682 (1995).
2. Pitti RM; Marsters SA; Ruppert S; Donahue CJ; Moore A; Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J. Biol. Chem. 271:12687-90 (1996).
3. Pan G; O'Rourke K; Chinnaiyan AM; O'Rourke K; Gentz R; Ebner R; Ni J; Dixit VM. The receptor for the cytotoxic ligand TRAIL. Science 276:111-113 (1997).
4. Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J. TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kB. Immunity 7:831-836 (1997).
5. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815-818 (1997).
6. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818-821 (1997).