Death Receptor Antibody Sampler Kit #8356

The tumor necrosis factor receptor family, which includes TNF-RI, Fas, DR3, DR4, DR5, and DR6, plays an important role in the regulation of apoptosis in various physiological systems (1,2). The receptors are activated by a family of cytokines that include TNF, FasL, and TRAIL. They are characterized by a highly conserved extracellular region containing cysteine-rich repeats and a conserved intracellular region of about 80 amino acids termed the death domain (DD). The DD is important for transducing the death signal by recruiting other DD containing adaptor proteins (FADD, TRADD, RIP) to the death-inducing signaling complex (DISC) resulting in activation of caspases. Death receptor signaling is also controlled by a family of decoy receptors (DcR1, DcR2, and DcR3) which lack a cytoplasmic DD and inhibit death receptor-mediated apoptosis by competing for ligand (3-5). The RIP (receptor-interacting protein) family of serine-threonine kinases (RIP, RIP2, RIP3, and RIP4) are important regulators of cellular stress that can trigger pro-survival and inflammatory responses through the activation of NF-κB as well as pro-apoptotic pathways (6). In addition to the kinase domain, RIP contains a death domain responsible for interaction with the death domain receptor Fas and for the recruitment to TNFR1 through interaction with TRADD (6,7). Overexpression of RIP induces both NF-κB activation and apoptosis (7,8). Caspase-8 dependent cleavage of the death domain on RIP can trigger the apoptotic activity of RIP (9). RIP-deficient cells show a failure in TNF-mediated NF-κB activation, making the cells more sensitive to apoptosis (10,11).