Death receptor 5 (DR5), also known asTRAIL receptor 2 (TRAILR2) andtumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is acell surface receptor of theTNF-receptor superfamily that bindsTRAIL and mediatesapoptosis.
The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces apoptosis signal. Mice have a homologous gene, tnfrsf10b, that has been essential in the elucidation of the function of this gene in humans. Studies with FADD-deficient mice suggested that FADD, adeath domain containingadaptor protein, is required for the apoptosis mediated by this protein.[5]
Monoclonal antibodies targeting DR5 have been developed and are currently under clinical trials for patients suffer from a variety of cancer types, seeTigatuzumab (CS-1008).
Luminescent iridium complex-peptide hybrids, serving as TRAIL mimics, have been designed, which target the death receptors DR4 and DR5 on cancer cells and induce their apoptosis.[12]
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Pai SI, Wu GS, Ozören N, Wu L, Jen J, Sidransky D, El-Deiry WS (Aug 1998). "Rare loss-of-function mutation of a death receptor gene in head and neck cancer".Cancer Research.58 (16):3513–8.PMID9721851.
Arai T, Akiyama Y, Okabe S, Saito K, Iwai T, Yuasa Y (Nov 1998). "Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas".Cancer Letters.133 (2):197–204.doi:10.1016/S0304-3835(98)00230-4.PMID10072170.
Mongkolsapaya J, Grimes JM, Chen N, Xu XN, Stuart DI, Jones EY, Screaton GR (Nov 1999). "Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation".Nature Structural Biology.6 (11):1048–53.doi:10.1038/14935.PMID10542098.S2CID6604122.