Tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)

TRAIL-R1, also known as DR4 and TNFRSF10A, is a cell surface receptor belonging to the TNF-receptor superfamily. It specifically binds to TRAIL and mediates apoptotic signaling. It is a type I transmembrane protein with an extracellular domain for ligand binding and a cytoplasmic death domain essential for transmitting apoptotic signals. TRAIL-R1 is mainly expressed on damaged, infected, and malignant cells and hematopoietic cells. Upon binding TRAIL, it triggers apoptosis via DISC formation and caspase activation. TRAIL-R1 is an attractive target for anticancer therapies, but clinical trials have shown limited efficacy due to resistance mechanisms. TRAIL/TRAIL-R interactions also regulate B cell selection during immune responses and may affect normal immune function. There are five human receptors for TRAIL, with only TRAIL-R1/DR4 and TRAIL-R2/DR5 possessing functional death domains. Key interacting partners include FADD and DAP3.

Other names

Death Receptor 4DR4TNFRSF10ATumor necrosis factor receptor superfamily member 10A

Binding of TRAIL-R1 to TRAIL leads to trimerization, recruitment of FADD, formation of DISC, activation of caspases, and induction of apoptosis.