Death receptor 4 explained

Death receptor 4 (DR4), also known as TRAIL receptor 1 (TRAILR1) and tumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.^{[1] [2]}

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis.^[3]

Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.^[4]

Interactions

TNFRSF10A has been shown to interact with DAP3.^[5]

Further reading

• Kimberley FC, Screaton GR . Following a TRAIL: update on a ligand and its five receptors. . Cell Res. . 14 . 5 . 359–72 . 2005 . 15538968 . 10.1038/sj.cr.7290236 . free .
• Fleury S, Thibodeau J, Croteau G . HLA-DR polymorphism affects the interaction with CD4. . J. Exp. Med. . 182 . 3 . 733–41 . 1995 . 7650480 . 10.1084/jem.182.3.733 . 2192178 . etal.
• MacFarlane M, Ahmad M, Srinivasula SM . Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. . J. Biol. Chem. . 272 . 41 . 25417–20 . 1997 . 9325248 . 10.1074/jbc.272.41.25417 . etal. free.
• Schneider P, Bodmer JL, Thome M . Characterization of two receptors for TRAIL. . FEBS Lett. . 416 . 3 . 329–34 . 1997 . 9373179 . 10.1016/S0014-5793(97)01231-3 . 83145771 . etal. free .
• Marsters SA, Sheridan JP, Pitti RM . A novel receptor for Apo2L/TRAIL contains a truncated death domain. . Curr. Biol. . 7 . 12 . 1003–6 . 1998 . 9382840 . 10.1016/S0960-9822(06)00422-2 . 21645158 . etal. free . 1997CBio....7.1003M .
• Chaudhary PM, Eby M, Jasmin A . Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. . Immunity . 7 . 6 . 821–30 . 1998 . 9430227 . 10.1016/S1074-7613(00)80400-8 . etal. free .
• Schneider P, Thome M, Burns K . TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. . Immunity . 7 . 6 . 831–6 . 1998 . 9430228 . 10.1016/S1074-7613(00)80401-X . etal. free .
• Diab BY, Lambert NC, L'Faqihi FE . Human collagen II peptide 256-271 preferentially binds to HLA-DR molecules associated with susceptibility to rheumatoid arthritis. . Immunogenetics . 49 . 1 . 36–44 . 1999 . 9811967 . 10.1007/s002510050461 . 22393348 . etal.
• Costanzo A, Guiet C, Vito P . c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB. . J. Biol. Chem. . 274 . 29 . 20127–32 . 1999 . 10400625 . 10.1074/jbc.274.29.20127 . free .
• Hymowitz SG, Christinger HW, Fuh G . Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. . Mol. Cell . 4 . 4 . 563–71 . 1999 . 10549288 . 10.1016/S1097-2765(00)80207-5 . etal. free .
• Gibson SB, Oyer R, Spalding AC . Increased expression of death receptors 4 and 5 synergizes the apoptosis response to combined treatment with etoposide and TRAIL. . Mol. Cell. Biol. . 20 . 1 . 205–12 . 2000 . 10594023 . 10.1128/MCB.20.1.205-212.2000. 85076 . etal.
• Miyazaki T, Reed JC . A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins. . Nat. Immunol. . 2 . 6 . 493–500 . 2001 . 11376335 . 10.1038/88684 . 6923467 .
• Trauzold A, Wermann H, Arlt A . CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells. . Oncogene . 20 . 31 . 4258–69 . 2001 . 11464292 . 10.1038/sj.onc.1204559 . etal. free .
• Dörr J, Bechmann I, Waiczies S . Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain. . J. Neurosci. . 22 . 4 . RC209 . 2002 . 11844843 . 10.1523/JNEUROSCI.22-04-j0001.2002. 6757573 . etal. free .
• Koyama S, Koike N, Adachi S . Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor. . J. Cancer Res. Clin. Oncol. . 128 . 2 . 73–9 . 2002 . 11862476 . 10.1007/s004320100292 . 19509629 .
• Guan B, Yue P, Lotan R, Sun SY . Evidence that the human death receptor 4 is regulated by activator protein 1. . Oncogene . 21 . 20 . 3121–9 . 2002 . 12082627 . 10.1038/sj.onc.1205430 . 6726601 .
• Söderström TS, Poukkula M, Holmström TH . Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. . J. Immunol. . 169 . 6 . 2851–60 . 2002 . 12218097 . 10.4049/jimmunol.169.6.2851. etal. free .

Notes and References

1. 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 . TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL . EMBO J . 16 . 17 . 5386–97 . Dec 1997 . 9311998 . 1170170 . 10.1093/emboj/16.17.5386 .
2. Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM . Arul Chinnaiyan . The receptor for the cytotoxic ligand TRAIL . Science . 276 . 5309 . 111–3 . April 1997 . 9082980 . 10.1126/science.276.5309.111 . 19984057 .
3. Web site: Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a.
4. Kuang AA, Diehl GE, Zhang J, Winoto A . FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. . J. Biol. Chem. . 275 . 33 . 25065–8 . 2000 . 10862756 . 10.1074/jbc.C000284200 . free .
5. Miyazaki . T . Reed J C . June 2001 . A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins . Nat. Immunol. . 2 . 6 . 493–500 . 1529-2908. 11376335 . 10.1038/88684 . 6923467 .