TNFRSF10AB

TNFRSF10AB is a gene symbol used in some genome annotations to denote the TRAIL receptor locus that includes the genes TNFRSF10A and TNFRSF10B. These genes encode the death receptors DR4 and DR5, which bind the TNF-related apoptosis-inducing ligand (TRAIL). The TNFRSF10A/ TNFRSF10B pair thus represents two closely related receptors that mediate TRAIL-induced signaling.

Both DR4 and DR5 are type I transmembrane proteins with extracellular cysteine-rich ligand-binding domains, a single transmembrane segment, and a cytoplasmic death domain that initiates apoptosis upon activation. Ligand binding promotes formation of the death-inducing signaling complex with FADD and caspase-8 (and sometimes caspase-10), triggering the extrinsic apoptotic cascade. DR5 has been reported as a transcriptional target of p53, linking cellular stress to TRAIL sensitivity; signaling can also engage non-apoptotic pathways depending on cellular context.

Expression of DR4 and DR5 is variable across tissues and cell types. Regulation is influenced by cellular stress, p53 status, and other signaling pathways. The TRAIL pathway can be modulated by decoy receptors TRAIL-R3 and TRAIL-R4, which can sequester TRAIL and dampen signaling. Alternative splicing may generate receptor isoforms with altered signaling properties.

Clinical relevance centers on the TRAIL-DR4/DR5 axis as a target for anticancer therapy. Agonist antibodies and recombinant TRAIL derivatives have been explored to selectively induce tumor cell apoptosis, though results have been variable and there are safety considerations for normal cells. Resistance mechanisms include reduced receptor expression, upregulation of anti-apoptotic proteins, and defects in death domain signaling. Ongoing research seeks combination strategies to improve selectivity and efficacy.