Death Receptor Signaling Pathway - Novus Apoptosis Research Series 3

Death receptors play an important role in the process of immune cell apoptosis, which induces apoptosis by binding to specific death ligands. Within a few seconds of binding of the death receptor to the ligand, the effector molecule aspartate cascade is activated and the cells are allowed to undergo apoptosis within a few hours.

TNF is a homotrimer composed of 157 amino acid subunits, mainly produced by activated macrophages. TNF mediates its biological activity through two cell surface receptors, TNFR-I and TNFR-II. The extracellular domains of these two TNFRs share homology, but TNFR-I contains DD, TNFR-II lacks DD, Both receptors can mediate apoptosis.

In 1995, Wiley et al. cloned a member of the TNF superfamily with high homology to apoptotic ligand 1 (Apo-1L) from a human myocardial cDNA library, named Apo-2L (Apoptosis-2 Ligand), a TNF-related Apoptotic ligand TRAIL. Two types of TRAIL receptors have been discovered, one being a functional receptor, such as TRAILR1 and TRAILR2, which contain a death domain and are referred to as death receptor 4 (DR4) and death receptor 5 (DR5), respectively. The other type is a non-functional receptor, such as TRAILR3, also known as trap receptor 1, TRAILR4, also known as trap receptor 2,. The extracellular structure of all receptors is highly homologous, and the non-functional receptor has an intracellular domain deleted, thus losing the function of mediating apoptosis. In the process of inducing apoptosis, TRAIL may not only activate a transcription factor, but also promote or inhibit the occurrence of apoptosis through the interaction between these transcription factors to achieve its selective cytotoxicity.