TNFRSF10C

TNFRSF10C, also known as TRAIL receptor 3 (TRAIL-R3), is a member of the tumor necrosis factor receptor (TNFR) superfamily encoded by the TNFRSF10C gene in humans. It is a type I transmembrane receptor that binds the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL).

Functionally, TRAIL-R3 acts as a decoy receptor. It binds TRAIL but does not transmit an apoptotic signal because its cytoplasmic region lacks a functional death domain. By sequestering TRAIL, it competes with death-inducing receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) and can modulate TRAIL-induced apoptosis, potentially influencing cell survival in various cellular contexts. The receptor may also participate in broader aspects of TRAIL signaling, although the precise mechanisms are not fully resolved.

Expression and regulation of TNFRSF10C show broad distribution across tissues, with expression patterns that can vary by cell type and physiological or pathological state. Alternative splicing has been described for TNFRSF10C, yielding multiple transcript variants and potentially distinct protein isoforms.

Clinical relevance of TNFRSF10C stems from its role in regulating TRAIL-mediated apoptosis, a pathway of interest in cancer biology and in therapies that employ TRAIL to induce tumor cell death. Altered expression levels or genetic variation in TNFRSF10C have been investigated for associations with cancer susceptibility or prognosis and with sensitivity to TRAIL-based treatments, though findings are not consistently reported across studies.

See also: TNFRSF10A, TNFRSF10B, TNFRSF10D, TRAIL pathway, death receptors.