TNFRSF10A

TNF receptor superfamily member 10a (TNFRSF10A) is referred to as death receptor 4 (DR4) and tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptor. Members of this family are type I transmembrane receptors, contain 1-5 cysteine-rich domains in their extracellular domain and an 80 amino acid death domain (DD) in the cytoplasmic tail which is essential for transduction of the death signal. TNFRSF10A is encoded by the TNFRSF10A gene and is located at 8p21-22. TNFRSF10A contains one single transmembrane helix as well as the apoptosis-triggering cytoplasmic death domain.

TNFRSF10A mediates TRAIL-induced apoptosis through their engagement and contributes to the enhancement of apoptosis triggered by anticancer drugs. The trimerized TNFRSF10A interact specifically with the adaptor protein FADD, which subsequently recruits the pro-caspase 8 through the death effector domain. Aggregation of pro-CASP8 leads to auto-cleavage and activation of caspase 8 and activates effector caspases such as caspase 3 and then induces apoptosis. Inhibition of cell death signaling due to alterations in TNFRSF10A involves deregulated cell proliferation and predisposes to cancer. The key elements of the DR4 ligand-binding
domain are encoded by exons 3 and 4.
Entrez Gene ID: 8797
UniProt ID: O00220