Death receptor 5

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, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.{{cite web | title = Entrez Gene: TNFRSF10B tumor necrosis factor receptor superfamily, member 10b| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8795}}

DR5 has been shown to interact with:

• Caspase 8,
• Caspase 10,{{cite journal | vauthors = MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES | date = Oct 1997 | title = Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL | journal = J. Biol. Chem. | volume = 272 | issue = 41 | pages = 25417–20 | pmid = 9325248 | doi = 10.1074/jbc.272.41.25417| doi-access = free}}
• FADD,{{cite journal | vauthors = Gajate C, Mollinedo F | date = Mar 2005 | title = Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy | journal = J. Biol. Chem. | volume = 280 | issue = 12 | pages = 11641–7 | pmid = 15659383 | doi = 10.1074/jbc.M411781200| doi-access = free }}{{cite journal | vauthors = Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L | date = Dec 1997 | title = Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway | journal = Immunity | volume = 7 | issue = 6 | pages = 821–30 | pmid = 9430227 | doi = 10.1016/s1074-7613(00)80400-8| doi-access = free }} and
• TRAIL.{{cite journal | vauthors = Kaptein A, Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen MJ, Bodmer JL, Tschopp J, Farrow SN | date = Nov 2000 | title = Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3) | journal = FEBS Lett. | volume = 485 | issue = 2–3 | pages = 135–41 | pmid = 11094155 | doi = 10.1016/s0014-5793(00)02219-5| s2cid = 38403545 | doi-access = free }}{{cite journal | vauthors = Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT | date = Sep 1997 | title = TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL | journal = EMBO J. | volume = 16 | issue = 17 | pages = 5386–97 | pmid = 9311998 | pmc = 1170170 | doi = 10.1093/emboj/16.17.5386}}{{cite journal | vauthors = Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM | date = Oct 1999 | title = Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5 | journal = Mol. Cell | volume = 4 | issue = 4 | pages = 563–71 | pmid = 10549288 | doi = 10.1016/S1097-2765(00)80207-5| doi-access = free }}

Monoclonal antibodies targeting DR5 have been developed and are currently under clinical trials for patients suffer from a variety of cancer types, see Tigatuzumab (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.{{cite journal | vauthors = Masum AA, Yokoi K, Hisamatsu Y, Naito K, Shashni B, Aoki S | title = Design and synthesis of a luminescent iridium complex-peptide hybrid (IPH) that detects cancer cells and induces their apoptosis | journal = Bioorganic & Medicinal Chemistry | volume = 26 | issue = 17 | pages = 4804–4816 | date = September 2018 | pmid = 30177492 | doi = 10.1016/j.bmc.2018.08.016 | s2cid = 52149418 }}

• Cluster of differentiation
• Tumor necrosis factor receptor
• Tigatuzumab

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Abe K, Kurakin A, Mohseni-Maybodi M, Kay B, Khosravi-Far R | title = The complexity of TNF-related apoptosis-inducing ligand | journal = Annals of the New York Academy of Sciences | volume = 926 | issue = 1 | pages = 52–63 | year = 2001 | pmid = 11193041 | doi = 10.1111/j.1749-6632.2000.tb05598.x | s2cid = 45991330 }}
• {{cite journal | vauthors = Cha SS, Song YL, Oh BH | title = Specificity of molecular recognition learned from the crystal structures of TRAIL and the TRAIL:sDR5 complex | journal = Vitamins and Hormones | volume = 67 | pages = 1–17 | year = 2004 | pmid = 15110168 | doi = 10.1016/S0083-6729(04)67001-4 | isbn = 978-0-12-709867-8 }}
• {{cite journal | vauthors = Kimberley FC, Screaton GR | title = Following a TRAIL: update on a ligand and its five receptors | journal = Cell Research | volume = 14 | issue = 5 | pages = 359–72 | date = Oct 2004 | pmid = 15538968 | doi = 10.1038/sj.cr.7290236 | doi-access = free }}
• {{cite journal | vauthors = Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM | title = An antagonist decoy receptor and a death domain-containing receptor for TRAIL | journal = Science | volume = 277 | issue = 5327 | pages = 815–8 | date = Aug 1997 | pmid = 9242610 | doi = 10.1126/science.277.5327.815 }}
• {{cite journal | vauthors = Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A | title = Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors | journal = Science | volume = 277 | issue = 5327 | pages = 818–21 | date = Aug 1997 | pmid = 9242611 | doi = 10.1126/science.277.5327.818 }}
• {{cite journal | vauthors = Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI | title = TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL | journal = Current Biology | volume = 7 | issue = 9 | pages = 693–6 | date = Sep 1997 | pmid = 9285725 | doi = 10.1016/S0960-9822(06)00297-1 | s2cid = 17740648 | doi-access = free | bibcode = 1997CBio....7..693S }}
• {{cite journal | vauthors = Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT | title = TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL | journal = The EMBO Journal | volume = 16 | issue = 17 | pages = 5386–97 | date = Sep 1997 | pmid = 9311998 | pmc = 1170170 | doi = 10.1093/emboj/16.17.5386 }}
• {{cite journal | vauthors = MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES | title = Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL | journal = The Journal of Biological Chemistry | volume = 272 | issue = 41 | pages = 25417–20 | date = Oct 1997 | pmid = 9325248 | doi = 10.1074/jbc.272.41.25417 | doi-access = free}}
• {{cite journal | vauthors = Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS | title = KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene | journal = Nature Genetics | volume = 17 | issue = 2 | pages = 141–3 | date = Oct 1997 | pmid = 9326928 | doi = 10.1038/ng1097-141 | s2cid = 7037468 }}
• {{cite journal | vauthors = Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J | title = Characterization of two receptors for TRAIL | journal = FEBS Letters | volume = 416 | issue = 3 | pages = 329–34 | date = Oct 1997 | pmid = 9373179 | doi = 10.1016/S0014-5793(97)01231-3 | s2cid = 83145771 | url = https://serval.unil.ch/resource/serval:BIB_25D695CC2FFE.P001/REF.pdf | doi-access = free }}
• {{cite journal | vauthors = Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, Ashkenazi A | title = A novel receptor for Apo2L/TRAIL contains a truncated death domain | journal = Current Biology | volume = 7 | issue = 12 | pages = 1003–6 | date = Dec 1997 | pmid = 9382840 | doi = 10.1016/S0960-9822(06)00422-2 | s2cid = 21645158 | doi-access = free | bibcode = 1997CBio....7.1003M }}
• {{cite journal | vauthors = Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L | title = Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway | journal = Immunity | volume = 7 | issue = 6 | pages = 821–30 | date = Dec 1997 | pmid = 9430227 | doi = 10.1016/S1074-7613(00)80400-8 | doi-access = free }}
• {{cite journal | vauthors = Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J | title = TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB | journal = Immunity | volume = 7 | issue = 6 | pages = 831–6 | date = Dec 1997 | pmid = 9430228 | doi = 10.1016/S1074-7613(00)80401-X | url = https://serval.unil.ch/notice/serval:BIB_1D571B98E298 | doi-access = free }}
• {{cite journal | vauthors = Pai SI, Wu GS, Ozören N, Wu L, Jen J, Sidransky D, El-Deiry WS | title = Rare loss-of-function mutation of a death receptor gene in head and neck cancer | journal = Cancer Research | volume = 58 | issue = 16 | pages = 3513–8 | date = Aug 1998 | pmid = 9721851 }}
• {{cite journal | vauthors = Arai T, Akiyama Y, Okabe S, Saito K, Iwai T, Yuasa Y | title = Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas | journal = Cancer Letters | volume = 133 | issue = 2 | pages = 197–204 | date = Nov 1998 | pmid = 10072170 | doi = 10.1016/S0304-3835(98)00230-4 }}
• {{cite journal | vauthors = Mongkolsapaya J, Grimes JM, Chen N, Xu XN, Stuart DI, Jones EY, Screaton GR | title = Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation | journal = Nature Structural Biology | volume = 6 | issue = 11 | pages = 1048–53 | date = Nov 1999 | pmid = 10542098 | doi = 10.1038/14935 | s2cid = 6604122 }}
• {{cite journal | vauthors = Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM | title = Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5 | journal = Molecular Cell | volume = 4 | issue = 4 | pages = 563–71 | date = Oct 1999 | pmid = 10549288 | doi = 10.1016/S1097-2765(00)80207-5 | doi-access = free }}
• {{cite journal | vauthors = Kuang AA, Diehl GE, Zhang J, Winoto A | title = FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts | journal = The Journal of Biological Chemistry | volume = 275 | issue = 33 | pages = 25065–8 | date = Aug 2000 | pmid = 10862756 | doi = 10.1074/jbc.C000284200 | doi-access = free }}
• {{cite journal | vauthors = Trauzold A, Wermann H, Arlt A, Schütze S, Schäfer H, Oestern S, Röder C, Ungefroren H, Lampe E, Heinrich M, Walczak H, Kalthoff H | title = CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells | journal = Oncogene | volume = 20 | issue = 31 | pages = 4258–69 | date = Jul 2001 | pmid = 11464292 | doi = 10.1038/sj.onc.1204559 | doi-access = free }}

{{refend}}

• {{MeshName|TNFRSF10B+protein,+human}}

{{NLM content}}

{{PDB Gallery|geneid=8795}}

{{Clusters of differentiation}}

{{Tumor necrosis factor receptor superfamily}}

{{Cytokine receptor modulators}}

Category:Clusters of differentiation

Category:TNF receptor family