Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D) (TNFRSF10D)

Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D), commonly known as Decoy Receptor 2 (DcR2), is a cell surface receptor that plays a pivotal role in regulating apoptosis [1, 5]. As a member of the TNFR superfamily, it binds to the TNF-related apoptosis-inducing ligand (TRAIL) but lacks a functional intracellular death domain, thereby acting as a decoy that sequesters TRAIL from pro-apoptotic receptors DR4 and DR5 [9, 12]. Beyond its role as a competitive inhibitor, DcR2 can actively signal through pathways such as NF-kappaB and Akt to promote cell survival and resistance to apoptosis [4, 15]. In clinical contexts, DcR2 is frequently overexpressed in various cancers, contributing to tumor evasion of immune-mediated cell death and resistance to TRAIL-based therapies [11, 14]. It is also recognized as a marker of cellular senescence and has been implicated in the progression of chronic diseases like renal fibrosis and acute kidney injury [6, 15]. Therapeutic strategies targeting DcR2 aim to inhibit its decoy function or downregulate its expression to sensitize cancer cells to apoptotic stimuli [1, 14].

Other names

Decoy receptor 2DcR2TRAIL receptor 4TRAIL-R4TRUNDDCD264

DcR2 functions as a decoy receptor by competitively binding to the TNF-related apoptosis-inducing ligand (TRAIL), thereby sequestering it from the pro-apoptotic death receptors DR4 and DR5 [1, 5, 9]. Unlike other decoy receptors, DcR2 possesses a truncated intracellular death domain that allows it to transduce anti-apoptotic signals through the activation of the NF-kappaB and Akt pathways, which promotes cell survival and resistance to apoptosis [4, 15]. By inhibiting the processing of procaspase-8 within the death-inducing signaling complex (DISC), DcR2 effectively blunts the extrinsic apoptotic pathway [13, 15].