DR4

Summary

Gene Symbol: DR4
Description: TNF receptor superfamily member 10a
Alias: APO2, CD261, DR4, TRAILR-1, TRAILR1, tumor necrosis factor receptor superfamily member 10A, TNF-related apoptosis-inducing ligand receptor 1, TRAIL receptor 1, TRAIL-R1, cytotoxic TRAIL receptor, death receptor 4, tumor necrosis factor receptor superfamily member 10a variant 2, tumor necrosis factor receptor superfamily, member 10a
Species: human
Products:     DR4

Top Publications

  1. Leverkus M, Sprick M, Wachter T, Denk A, Bröcker E, Walczak H, et al. TRAIL-induced apoptosis and gene induction in HaCaT keratinocytes: differential contribution of TRAIL receptors 1 and 2. J Invest Dermatol. 2003;121:149-55 pubmed
    ..By employing receptor-specific blocking antibodies we demonstrate that TRAIL receptor 1 plays the primary role in mediating caspase activation and apoptosis in HaCaT cells...
  2. Wang M, Wang M, Cheng G, Zhang Z, Fu G, Zhang Z. Genetic variants in the death receptor 4 gene contribute to susceptibility to bladder cancer. Mutat Res. 2009;661:85-92 pubmed publisher
    b>Death receptor 4 (DR4) is an important mediator of apoptosis, and its dysfunction may be related to carcinogenesis and cancer development...
  3. Zhang Y, Zhang B. TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res. 2008;6:1861-71 pubmed publisher
    ..are being evaluated clinically as anticancer therapies, selectively kill cancer cells through the death receptors DR4 and DR5. However, their therapeutic potential is limited by occurring resistance in tumor cells...
  4. Wolf S, Mertens D, Pscherer A, Schroeter P, Winkler D, Grone H, et al. Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer. Int J Cancer. 2006;118:1831-5 pubmed
    ..The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683A-->C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies. ..
  5. Chaudhary P, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L. Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity. 1997;7:821-30 pubmed
    b>Death receptor 4 (DR4) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD-independent pathway to induce apoptosis and does not activate the NF-kappaB pathway...
  6. Hazra A, Chamberlain R, Grossman H, Zhu Y, Spitz M, Wu X. Death receptor 4 and bladder cancer risk. Cancer Res. 2003;63:1157-9 pubmed
    ..factor-related apoptosis-inducing ligand stimulates the extrinsic apoptoticpathway by binding to death receptors 4 (DR4) and 5 (DR5)...
  7. Bavi P, Prabhakaran S, Abubaker J, Qadri Z, George T, Al Sanea N, et al. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations. Mol Cancer. 2010;9:203 pubmed publisher
    ..necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5)...
  8. Dorr J, Bechmann I, Waiczies S, Aktas O, Walczak H, Krammer P, et al. Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain. J Neurosci. 2002;22:RC209 pubmed
    ..Conversely, this death receptor-ligand system might well play an important role in T cell-mediated autoimmune diseases of the CNS such as multiple sclerosis. ..
  9. Jin Z, Li Y, Pitti R, Lawrence D, Pham V, Lill J, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 2009;137:721-35 pubmed publisher
    Cell-surface death receptors such as DR4 and DR5 trigger apoptosis through a death-inducing signaling complex (DISC) that recruits the apical protease caspase-8...

More Information

Publications82

  1. Ulybina Y, Kuligina E, Mitiushkina N, Rozanov M, Ivantsov A, Ponomariova D, et al. Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer. Cancer Lett. 2009;278:183-191 pubmed publisher
    ..07-5.69), p=0.03; His-carriers for Casp8 His302Asp: OR=2.26 (95% CI: 1.18-4.31), p=0.02; Arg-carriers for DR4 Lys441Arg: OR=1.89 (95% CI: 1.05-3.40), p=0.03), and therefore were selected for the validation...
  2. Kuang A, Diehl G, 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. 2000;275:25065-8 pubmed
    ..TRAIL-induced apoptosis in humans is mediated by its receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2)...
  3. Kriegl L, Jung A, Engel J, Jackstadt R, Gerbes A, Gallmeier E, et al. Expression, cellular distribution, and prognostic relevance of TRAIL receptors in hepatocellular carcinoma. Clin Cancer Res. 2010;16:5529-38 pubmed publisher
    ..The fraction of HCC samples with positive membrane staining for TRAIL receptor 1 (TRAIL-R1) and 2 (TRAIL-R2) was 1.4- and 2...
  4. MacFarlane M, Inoue S, Kohlhaas S, Majid A, Harper N, Kennedy D, et al. Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1. Cell Death Differ. 2005;12:773-82 pubmed
    ..Thus combination of an agonistic TRAIL-R1 Ab and an HDACi, such as the anticonvulsant sodium valproate, could be of value in treating CLL. ..
  5. Chen B, Liu S, Wang X, Xu W, Li Y, Zhao W, et al. TRAIL-R1 polymorphisms and cancer susceptibility: an evidence-based meta-analysis. Eur J Cancer. 2009;45:2598-605 pubmed publisher
    ..data on the association between tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 or DR4) polymorphisms rs20575 (C626G), rs2230229 (A1322G) and rs20576 (A683C) and cancer risk are inconclusive...
  6. Zhu H, Dong H, Eksioglu E, Hemming A, Cao M, Crawford J, et al. Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system. Gastroenterology. 2007;133:1649-59 pubmed
    ..to be triggered by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, death receptor 4 and death receptor 5, which were up-regulated in HCV infection...
  7. Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Roder C, et al. TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. J Mol Med (Berl). 2010;88:729-40 pubmed publisher
    Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and agonistic anti-DR4/TRAIL-R1 and anti-DR5/TRAIL-R2 antibodies are currently under clinical investigation for treatment of different malignancies...
  8. Korner C, Riesner K, Kramer B, Eisenhardt M, Glässner A, Wolter F, et al. TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients. BMC Cancer. 2012;12:85 pubmed publisher
    ..To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (..
  9. van de Kooij B, Verbrugge I, de Vries E, Gijsen M, Montserrat V, Maas C, et al. Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1. J Biol Chem. 2013;288:6617-28 pubmed publisher
    ..These findings reveal that endogenous MARCH-8 regulates the steady-state cell surface expression of TRAIL-R1. ..
  10. Walczak H, Degli Esposti M, Johnson R, Smolak P, Waugh J, Boiani N, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 1997;16:5386-97 pubmed
    ..Based on homology searching of a private database, a receptor for TRAIL (DR4 or TRAIL-R1) was recently identified...
  11. Tastemir Korkmaz D, Demirhan O, Kuleci S, Hasturk S. There is no significant association between death receptor 4 (DR4) gene polymorphisms and lung cancer in Turkish population. Pathol Oncol Res. 2013;19:779-84 pubmed publisher
    b>Death receptor 4 (DR4) gene is a candidate tumor suppressor gene that has a role in apoptotic pathway. It was reported in literature that polymorphisms in DR4 gene lead to susceptibility to many cancers...
  12. Frank B, Hemminki K, Shanmugam K, Meindl A, Klaes R, Schmutzler R, et al. Association of death receptor 4 haplotype 626C-683C with an increased breast cancer risk. Carcinogenesis. 2005;26:1975-7 pubmed
    ..necrosis factor-related apoptosis-inducing ligand stimulates the extrinsic apoptotic pathway by binding to death receptor 4 (DR4)...
  13. Sanlioglu A, Dirice E, Elpek O, Korcum A, Ozdogan M, Suleymanlar I, et al. High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients. Pancreas. 2009;38:154-60 pubmed publisher
  14. Pan G, O Rourke K, Chinnaiyan A, Gentz R, Ebner R, Ni J, et al. The receptor for the cytotoxic ligand TRAIL. Science. 1997;276:111-3 pubmed
    ..receptor for TRAIL was found to be an undescribed member of the TNF-receptor family (designated death receptor-4, DR4) that contains a cytoplasmic "death domain" capable of engaging the cell suicide apparatus but not the ..
  15. van Geelen C, Westra J, de Vries E, Boersma van Ek W, Zwart N, Hollema H, et al. Prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand and its receptors in adjuvantly treated stage III colon cancer patients. J Clin Oncol. 2006;24:4998-5004 pubmed
    ..Therefore, the prognostic relevance was analyzed of the expression of TRAIL and its death receptors DR4 and DR5 on disease-free survival and overall survival in stage III colon cancer patients treated with adjuvant ..
  16. Horak P, Pils D, Roessler M, Tomek S, Elandt K, Zeillinger R, et al. Common death receptor 4 (DR4) polymorphisms do not predispose to ovarian cancer. Gynecol Oncol. 2005;97:514-8 pubmed
    Polymorphisms of death receptor 4 (DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death, promoting tumor development and progression...
  17. Kimberley F, Screaton G. Following a TRAIL: update on a ligand and its five receptors. Cell Res. 2004;14:359-72 pubmed
    ..This review takes a comprehensive look at the story of this enigmatic ligand, addressing its remaining potential as a therapeutic and providing an overview of the TRAIL receptors themselves. ..
  18. Pavet V, Beyrath J, Pardin C, Morizot A, Lechner M, Briand J, et al. Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity. Cancer Res. 2010;70:1101-10 pubmed publisher
    ..trials are exploring anticancer approaches based on signaling by TRAIL, a ligand for the cell death receptors DR4 and DR5...
  19. van Geelen C, Pennarun B, Le P, de Vries E, de Jong S. Modulation of TRAIL resistance in colon carcinoma cells: different contributions of DR4 and DR5. BMC Cancer. 2011;11:39 pubmed publisher
    ..the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance...
  20. Ouyang W, Yang C, Liu Y, Xiong J, Zhang J, Zhong Y, et al. Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells. Int J Oncol. 2011;39:1577-86 pubmed publisher
    ..cell line, TRAIL-resistant A549 cell line showed a similar expression level of DR5 and a higer expression level of DR4. It indicates that there is no positive correlation between the expression levels of death receptors and ..
  21. Sun R, Zhang Y, Lv Q, Liu B, Jin M, Zhang W, et al. Toll-like receptor 3 (TLR3) induces apoptosis via death receptors and mitochondria by up-regulating the transactivating p63 isoform alpha (TAP63alpha). J Biol Chem. 2011;286:15918-28 pubmed publisher
    ..Taken together, TAp63? is a crucial regulator downstream of TLR3 to induce cell death via death receptors and mitochondria. ..
  22. Thomas L, Johnson R, Reed J, Thorburn A. The C-terminal tails of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas receptors have opposing functions in Fas-associated death domain (FADD) recruitment and can regulate agonist-specific mechanisms of receptor activation. J Biol Chem. 2004;279:52479-86 pubmed
    ..TNF) superfamily of receptors such as Fas/CD95 and the TNF-related apoptosis-inducing ligand (TRAIL) receptors DR4 and DR5 induce apoptosis by recruiting adaptor molecules and caspases...
  23. Oikonomou E, Kosmidou V, Katseli A, Kothonidis K, Mourtzoukou D, Kontogeorgos G, et al. TRAIL receptor upregulation and the implication of KRAS/BRAF mutations in human colon cancer tumors. Int J Cancer. 2009;125:2127-35 pubmed publisher
    ..Higher expression of its pro-death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) attenuates higher sensitivity to TRAIL-induced apoptosis, and represents a marker for better ..
  24. Horak P, Pils D, Haller G, Pribill I, Roessler M, Tomek S, et al. Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol Cancer Res. 2005;3:335-43 pubmed
    ..2, a region frequently deleted in ovarian cancer. Lack of expression of TRAIL receptor 1 (death receptor 4, DR4) correlates with resistance to TRAIL-induced apoptosis in ovarian cancer cells...
  25. Herbeuval J, Grivel J, Boasso A, Hardy A, Chougnet C, Dolan M, et al. CD4+ T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis. Blood. 2005;106:3524-31 pubmed
    ..We propose a novel model in which a type 1 IFN-regulated TRAIL /DR5 mechanism induces apoptosis of HIV-1-exposed CD4(+) T cells. ..
  26. Frank B, Shanmugam K, Beckmann L, Hemminki K, Brenner H, Hoffmeister M, et al. Death receptor 4 variants and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:2002-5 pubmed
    ..factor-related apoptosis-inducing ligand receptor modulates apoptotic response by binding to the proapoptotic death receptor 4 (DR4)...
  27. Kuraoka K, Matsumura S, Sanada Y, Nakachi K, Imai K, Eguchi H, et al. A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan. Oncol Rep. 2005;14:465-70 pubmed
    b>Death receptor 4 (DR4) is a member of the tumor necrosis factor-related apoptosis-inducing ligand receptor genes...
  28. Drosopoulos K, Roberts M, Cermak L, Sasazuki T, Shirasawa S, Andera L, et al. Transformation by oncogenic RAS sensitizes human colon cells to TRAIL-induced apoptosis by up-regulating death receptor 4 and death receptor 5 through a MEK-dependent pathway. J Biol Chem. 2005;280:22856-67 pubmed
    ..ligand (TRAIL) is able to kill specific tumor cells through the engagement of its receptors, death receptor 4 (DR4) and death receptor 5 (DR5), and the activation of apoptotic pathways, providing promising targets for ..
  29. Mittal R, Srivastava P, Mittal T, Verma A, Jaiswal P, Singh V, et al. Association of death receptor 4, Caspase 3 and 5 gene polymorphism with increased risk to bladder cancer in North Indians. Eur J Surg Oncol. 2011;37:727-33 pubmed publisher
    Perturbed apoptosis due to missense alterations in candidate tumor suppressor gene Death receptor 4 (DR4) and in caspases (Casp) lead to deregulated cell proliferation and cancer predisposition...
  30. Shishodia G, Koul S, Dong Q, Koul H. Tetrandrine (TET) Induces Death Receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5) and Sensitizes Prostate Cancer Cells to TRAIL-Induced Apoptosis. Mol Cancer Ther. 2018;17:1217-1228 pubmed publisher
    ..TRAIL-induced apoptosis, and they do so by upregulating mRNA expression and protein levels of death receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5)...
  31. 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. 1999;274:20127-32 pubmed
    ..In transfection experiments c-E10 oligomerizes, binds to the cytoplasmic portion of TRAIL receptor 1 (DR4) and coprecipitates with TRADD...
  32. Dyari H, Rawling T, Chen Y, Sudarmana W, Bourget K, Dwyer J, et al. A novel synthetic analogue of ω-3 17,18-epoxyeicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells. FASEB J. 2017;31:5246-5257 pubmed publisher
    ..Silencing of the death receptor TNF receptor 1 (TNFR1), but not Fas, DR4, or DR5, and the adapters TRADD and TNF receptor-associated factor 2, but not Fas-associated death domain, ..
  33. Pal S, Tifrea D, Zhong G, de la Maza L. Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice. Infect Immun. 2018;86: pubmed publisher
    ..in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4)...
  34. Li X, Wu B, Chen L, Ju Y, Li C, Meng S. Urokinase-type plasminogen activator receptor inhibits apoptosis in triple-negative breast cancer through miR-17/20a suppression of death receptors 4 and 5. Oncotarget. 2017;8:88645-88657 pubmed publisher
    ..We found that depletion of uPAR by RNAi increases death receptor 4 (DR4) and death receptor 5 (DR5) expression and triggers TRAIL-induced apoptosis in TNBC cells...
  35. Majji S, Wijayalath W, Shashikumar S, Brumeanu T, Casares S. Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity. Malar J. 2018;17:114 pubmed publisher
    ..The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO...
  36. Kurbanov B, Fecker L, Geilen C, Sterry W, Eberle J. Resistance of melanoma cells to TRAIL does not result from upregulation of antiapoptotic proteins by NF-kappaB but is related to downregulation of initiator caspases and DR4. Oncogene. 2007;26:3364-77 pubmed
    ..time that TRAIL-induced activation of NF-kappaB occurs in apoptosis-sensitive melanoma cell lines through TRAIL receptor 1/death receptor 4 (TRAIL-R1/DR4), whereas TRAIL failed to activate nuclear factor kappa B (NF-kappaB) in ..
  37. Clancy L, Mruk K, Archer K, Woelfel M, Mongkolsapaya J, Screaton G, et al. Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis. Proc Natl Acad Sci U S A. 2005;102:18099-104 pubmed
    ..We propose that TR4 is a "regulatory" rather than "decoy" receptor that inhibits apoptosis signaling by TRAIL through this previously uncharacterized ligand-independent mechanism. ..
  38. Arnoux F, Mariot C, Peen E, Lambert N, Balandraud N, Roudier J, et al. Peptidyl arginine deiminase immunization induces anticitrullinated protein antibodies in mice with particular MHC types. Proc Natl Acad Sci U S A. 2017;114:E10169-E10177 pubmed publisher
    ..hapten/carrier immunization, we immunized DBA/2 mice (whose IE?d chain is similar to that of HLA-DRB1*04:02, an HLA-DR4 subtype not associated with RA). DBA/2 mice failed to develop antibodies to citrullinated fibrinogen peptides...
  39. Yang J, Li G, Zhang K. Pro-survival effects by NF-?B, Akt and ERK(1/2) and anti-apoptosis actions by Six1 disrupt apoptotic functions of TRAIL-Dr4/5 pathway in ovarian cancer. Biomed Pharmacother. 2016;84:1078-1087 pubmed publisher
    Apoptotic signaling provoked by death receptors, DR4 and DR5, are generally considered to promote cell death and chemosensitivity in multiple cancers, but this view is being thrown into doubt with recent findings that up-regulated DR4 ..
  40. Fahrioğlu U, Dodurga Y, Elmas L, Seçme M. Ferulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro. Gene. 2016;576:476-82 pubmed publisher
    ..as CCND1 (cyclin D1),CDK4, CDK6, RB, p21, p16, p53, caspase-3, caspase-9, caspase-8, caspase-10, Bcl-2, BCL-XL,BID, DR4,DR5,FADD,TRADD,PARP, APAF, Bax, Akt, PTEN, PUMA, NOXA, MMP2, MMP9, TIMP1 and TIMP2 were determined by real-time PCR...
  41. Park C, Lee W, Han M, Song K, Hong S, Nagappan A, et al. Lonicera japonica Thunb. Induces caspase-dependent apoptosis through death receptors and suppression of AKT in U937 human leukemic cells. Phytother Res. 2017;: pubmed publisher
    ..Here, we demonstrated that PELJ induced apoptosis by upregulation of DR4 and Fas, and further it is augmented by suppression of XIAP...
  42. Zhang M, Wang J, Jia L, Huang J, He C, Hu F, et al. Transmembrane TNF-? promotes activation-induced cell death by forward and reverse signaling. Oncotarget. 2017;8:63799-63812 pubmed publisher
    ..TNF-related apoptosis-inducing ligand and tmTNF-? to amplify AICD, and promoted activated T cells expressing death receptor 4, TNF receptor (TNFR) 1 and TNFR2 to enhance their sensitivity to AICD...
  43. Booth L, Roberts J, Sander C, Lee J, Kirkwood J, Poklepovic A, et al. The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo. Oncotarget. 2017;8:16367-16386 pubmed publisher
    ..inhibitor pazopanib interacted to activate: an eIF2?-Beclin1 pathway causing autophagosome formation; an eIF2?-DR4/DR5/CD95 pathway; and an eIF2?-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL...
  44. Guillaume Y, André C. Comparative binding to DR4 and DR5 receptors of TRAIL and BNNTs/PAHE/mPEG-DSPE/TRAIL nanoparticles. J Mol Recognit. 2017;30: pubmed publisher
    ..of cytokines, which induces apoptosis of cancer cells, thanks to its binding to its cognate receptors DR5 and DR4. We have recently demonstrated that nanovectorization of TRAIL with single-walled carbon nanotubes enhanced TRAIL ..
  45. Wong J, Quinn C, Brown A. SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR. Biochem J. 2006;400:485-91 pubmed
    ..By contrast, these responses were completely ablated when the DR4 element to which LXR binds was mutated...
  46. Gallmeier E, Bader D, Kriegl L, Berezowska S, Seeliger H, Goke B, et al. Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery. PLoS ONE. 2013;8:e56760 pubmed publisher
    ..This hypothesis should be evaluated in future clinical trials. ..
  47. Zhou Y, Peng Y, Mao Q, Li X, Chen M, Su J, et al. Casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells. Asian Pac J Trop Med. 2013;6:372-8 pubmed publisher
    ..Bcl-2/Bcl-XL/XIAP/Bid/DR5 and DR4 proteins were analyzed using western blot...
  48. Hou L, Zhang H, Xu P, Zhang L, Zhang X, Sun Y, et al. Effect of vitamin E succinate on the expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor in gastric cancer cells and CD4(+) T cells. Mol Biosyst. 2015;11:3119-28 pubmed publisher
    ..Moreover, the activation of the TRAIL receptor, death receptor 4 (DR4), and death receptor 5 (DR5) in gastric cancer cells increased for up to 12 h...
  49. Hayashi M, Abe K, Imaizumi H, Okai K, Kanno Y, Takahashi A, et al. Drug-induced liver injury with autoimmune features complicated with hemophagocytic syndrome. Clin J Gastroenterol. 2016;9:150-5 pubmed publisher
    ..supplement use, negative viral hepatitis markers, positive antinuclear antibody test, high IgG level, positive HLA-DR4, liver biopsy findings of centrizonal necrosis, and inflammatory cell infiltration in the portal area, she was ..
  50. Li J, Shen Q, Peng R, Chen R, Jiang P, Li Y, et al. Plumbagin enhances TRAIL-mediated apoptosis through up-regulation of death receptor in human melanoma A375 cells. J Huazhong Univ Sci Technolog Med Sci. 2010;30:458-63 pubmed publisher
    ..The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry...
  51. Marsters S, Sheridan J, Pitti R, Huang A, Skubatch M, Baldwin D, et al. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol. 1997;7:1003-6 pubmed
    b>Apo2 ligand (Apo2L [1], also called TRAIL for tumor necrosis factor (TNF)-related apoptosis-inducing ligand [2]) belongs to the TNF family and activates apoptosis in tumor cells...
  52. Ranjan S, Goihl A, Kohli S, Gadi I, Pierau M, Shahzad K, et al. Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells. Nat Commun. 2017;8:311 pubmed publisher
    ..Preincubation of human T-cells (HLA-DR4-CD4+) with aPC prior to transplantation into humanized (NSG-AB°DR4) mice ameliorates graft-..
  53. Kim K, Park U, Wang J, Lee J, Park S, Kim S, et al. Gene profiling of colonic serrated adenomas by using oligonucleotide microarray. Int J Colorectal Dis. 2008;23:569-80 pubmed publisher
  54. Ramamurthy V, Yamniuk A, Lawrence E, Yong W, Schneeweis L, Cheng L, et al. The structure of the death receptor 4-TNF-related apoptosis-inducing ligand (DR4-TRAIL) complex. Acta Crystallogr F Struct Biol Commun. 2015;71:1273-81 pubmed publisher
    The structure of death receptor 4 (DR4) in complex with TNF-related apoptosis-inducing ligand (TRAIL) has been determined at 3 Å resolution and compared with those of previously determined DR5-TRAIL complexes...
  55. Tımırcı Kahraman Ö, Ozkan N, Turan S, Farooqi A, Verim L, Ozturk T, et al. Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand and death receptor genes contribute to susceptibility to bladder cancer. Genet Test Mol Biomarkers. 2015;19:309-15 pubmed publisher
    ..the role of polymorphisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes in bladder cancer susceptibility in a Turkish population...
  56. Basu A, Haldar S. Anti-proliferative and proapoptotic effects of benzyl isothiocyanate on human pancreatic cancer cells is linked to death receptor activation and RasGAP/Rac1 down-modulation. Int J Oncol. 2009;35:593-9 pubmed
    ..Indeed, cell surface receptor analysis by flow cytometry demonstrates the up-regulation of DR4, a member of death receptor family in BITC exposed pancreatic cancer cells...
  57. Behrens M, Luckey D, Luthra H, David C, Taneja V. B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice. Clin Immunol. 2017;178:10-19 pubmed publisher
    ..Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice...
  58. Rizza S, Cummins N, Rider D, Saeed S, Klein M, Badley A. Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 is associated with poor viral response to interferon-based hepatitis C virus therapy in HIV/hepatitis C virus-coinfected individuals. AIDS. 2010;24:2639-44 pubmed publisher
    ..91 (95% confidence interval 1.63-21.38, P = 0.007)]. The rs4242392 SNP of the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 gene predicted poor interferon-based HCV treatment response in HIV/HCV-coinfected patients. ..
  59. Ullenhag G, Al Attar A, Mukherjee A, Green A, Ellis I, Durrant L. The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis. J Cancer Res Clin Oncol. 2015;141:505-14 pubmed publisher
    ..Over-expression of FLIP(T) but not TRAIL-R1, TRAIL-R2 or FLIP(L) provides stage-independent prognostic information in breast cancer patients. This indicates a clinically less aggressive phenotype. ..
  60. Jeong M, Lee E, Seong D, Seo J, Kim J, Grootjans S, et al. USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability. Oncogene. 2017;36:458-470 pubmed publisher
    ..Taken together, our data indicate that USP8 functions as a novel deubiquitylase of FLIPL and inhibits extrinsic apoptosis by stabilizing FLIPL. ..
  61. Langsenlehner T, Langsenlehner U, Renner W, Kapp K, Krippl P, HOFMANN G, et al. The Glu228Ala polymorphism in the ligand binding domain of death receptor 4 is associated with increased risk for prostate cancer metastases. Prostate. 2008;68:264-8 pubmed publisher
    b>Death receptor 4, encoded by the TNFRSF10A gene, is an important mediator of apoptosis and its dysfunction may be related to cancer development and distant tumor spread...
  62. Dabrowska A, Kim N, Aldovini A. Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol. 2008;181:8460-77 pubmed
    ..The induction of Egr1 and FOXO3a and its target genes was observed in Jurkat cells transduced by Tat alone. Tat-dependent activation of the Egr1-PTEN-FOXO3a pathway provides a mechanism for HIV-1-associated CD4(+) T cell death. ..
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    ..However, the molecular mediators of apoptosis in the intervertebral disk are poorly understood. Fas/FasL, TRAIL/DR4, TRAIL/DR5 and TNF-alpha/TNFR1 are ligand/receptor pairs of the tumor necrosis factor/nerve growth factor family, ..
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    ..The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase ..
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    ..Together these data identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, that is, the enzyme activated in an atypical complex down-regulates NF-kappaB activity through RIP1 cleavage. ..
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    ..constitute a subgroup of the tumor necrosis factor receptor (TNFR) superfamily, which includes TNFR1, Fas, DR4, and DR5...
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    ..588; P=0.018; OR=1.838; 95% CI: 1.105-3.057). It was concluded that the high frequency of 196R allele in the functional M196R polymorphism of TNFR2 is a risk factor for acne vulgaris in Han Chinese. ..
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    ..and enhancement of fas-associated protein with death domain (FADD), death-inducing signaling complex (DISC), death receptor 4 (DR) 4 and DR5, respectively. Reactive oxygen species (ROS) generation, up to 39.86±2...
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    ..4%). In addition, the TAP2*0101-1693.A allele showed significant (r = 0.45, p < 0.0003) association with HLA-DR4 only in RA patients and the prevalence of both TAP2*0101-1693...
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    ..three highly conserved sites by Akt, and only the phosphorylated MADD can directly interact with the TRAIL receptor DR4 thereby preventing Fas-associated death domain recruitment...
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    ..Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2R?c KO...
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    ..TRAIL-R1/DR4 protein expression was enhanced in Hep G2.2.15 cells as compared to Hep G2 cells...
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    TRAIL, a ligand of the TNFalpha family, induces upon binding to its pro-death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 the apoptosis of cancer cells...