Gene Symbol: Tnfrsf10b
Description: tumor necrosis factor receptor superfamily, member 10b
Alias: DR5, KILLER, Ly98, TRAILR2, TRICK2A, TRICK2B, TRICKB, tumor necrosis factor receptor superfamily member 10B, KILLER/DR5 TRAIL death-inducing receptor, death receptor 5
Species: mouse
Products:     Tnfrsf10b

Top Publications

  1. Diehl G, Yue H, Hsieh K, Kuang A, Ho M, Morici L, et al. TRAIL-R as a negative regulator of innate immune cell responses. Immunity. 2004;21:877-89 pubmed
    ..These data suggest that TRAIL-R negatively regulates innate immune responses. ..
  2. Finnberg N, Gruber J, Fei P, Rudolph D, Bric A, Kim S, et al. DR5 knockout mice are compromised in radiation-induced apoptosis. Mol Cell Biol. 2005;25:2000-13 pubmed
    DR5 (also called TRAIL receptor 2 and KILLER) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (also called TRAIL and Apo2 ligand)...
  3. Takeda K, Kojima Y, Ikejima K, Harada K, Yamashina S, Okumura K, et al. Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease. Proc Natl Acad Sci U S A. 2008;105:10895-900 pubmed publisher
    ..article, we show that the death signal mediated by TNF-related apoptosis-inducing ligand (TRAIL) receptor 2/death receptor 5 (DR5) may be a key regulator of cholestatic liver injury...
  4. 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)...
  5. Griffith T, Brincks E, Gurung P, Kucaba T, Ferguson T. Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells. J Immunol. 2011;186:791-8 pubmed publisher
    ..Unlike wild-type mice, Trail(-/-) or Dr5(-/-) mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent ..
  6. Brincks E, Katewa A, Kucaba T, Griffith T, Legge K. CD8 T cells utilize TRAIL to control influenza virus infection. J Immunol. 2008;181:4918-25 pubmed
    ..Furthermore, TRAIL expression occurs selectively on influenza-specific CD8(+) T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells...
  7. Wu G, Burns T, Zhan Y, Alnemri E, El Deiry W. Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. Cancer Res. 1999;59:2770-5 pubmed
    ..We report here the cloning of the mouse homologue of the TRAIL receptor KILLER/DR5 (MK). The cDNA of MK is 1146 bp in length and encodes a protein of 381 amino acids...
  8. Gurung P, Kucaba T, Schoenberger S, Ferguson T, Griffith T. TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion. J Leukoc Biol. 2010;88:1217-25 pubmed publisher
    ..deletion by soluble OVA???????, B6 mice were unresponsive to challenge after CFA/OVA immunization, and Trail?/? or Dr5?/? mice were immune, although all strains displayed similar OT-II peripheral deletion...
  9. Kawakubo T, Okamoto K, Iwata J, Shin M, Okamoto Y, Yasukochi A, et al. Cathepsin E prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface. Cancer Res. 2007;67:10869-78 pubmed
    ..These results thus indicate that cathepsin E plays a substantial role in host defense against tumor cells through TRAIL-dependent apoptosis and/or tumor-associated macrophage-mediated cytotoxicity. ..

Scientific Experts

More Information


  1. Liu Y, Liu S, Liang X, Zhang Q, Gao L, Han L, et al. Blockade of TRAIL pathway ameliorates HBV-induced hepatocyte apoptosis in an acute hepatitis model. Biochem Biophys Res Commun. 2007;352:329-34 pubmed
    ..In this study, we used a recombinant human soluble death receptor 5 (sDR5) to explore its effect in a mouse model of HBV-induced acute hepatitis...
  2. Pillai M, Collison L, Wang X, Finkelstein D, Rehg J, Boyd K, et al. The plasticity of regulatory T cell function. J Immunol. 2011;187:4987-97 pubmed publisher
    ..These data reveal that cross-regulatory pathways exist that control the utilization of suppressive mechanisms, thereby providing T(reg) functional plasticity. ..
  3. Gottwald L, Szwalski J, Piekarski J, Pasz Walczak G, Kubiak R, Spych M, et al. Membrane expression of the death ligand trail receptors DR4 and DR5 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer. J Obstet Gynaecol. 2013;33:512-8 pubmed publisher
    To assess membrane expression of DR4 and DR5 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the study examined 101 patients: 20 NE, 14 EAH and 67 EEC...
  4. Nguyen V, Cudrici C, Zernetkina V, Niculescu F, Rus H, Drachenberg C, et al. TRAIL, DR4 and DR5 are upregulated in kidneys from patients with lupus nephritis and exert proliferative and proinflammatory effects. Clin Immunol. 2009;132:32-42 pubmed publisher
    ..We demonstrate here that TRAIL, DR4 and DR5 are upregulated in proximal and distal tubules of patients with proliferative lupus nephritis...
  5. Farrell G, Larter C, Hou J, Zhang R, Yeh M, Williams J, et al. Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression. J Gastroenterol Hepatol. 2009;24:443-52 pubmed publisher
    ..However, murine TRAIL receptors, particularly decoyTRAIL-R1/TNFRSFH23 and Killer/DR5 mRNA increased...
  6. O FLAHERTY J, Mei Y, Freer M, Weyman C. Signaling through the TRAIL receptor DR5/FADD pathway plays a role in the apoptosis associated with skeletal myoblast differentiation. Apoptosis. 2006;11:2103-13 pubmed
    ..treatment with a soluble TRAIL decoy receptor or expression of a dominant-negative mutant of the TRAIL receptor DR5 abrogated apoptosis...
  7. Cazanave S, Mott J, Bronk S, Werneburg N, Fingas C, Meng X, et al. Death receptor 5 signaling promotes hepatocyte lipoapoptosis. J Biol Chem. 2011;286:39336-48 pubmed publisher
    ..Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5) is significantly elevated in patients with nonalcoholic steatohepatitis, and steatotic hepatocytes ..
  8. Steinwede K, Henken S, Bohling J, Maus R, Ueberberg B, Brumshagen C, et al. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice. J Exp Med. 2012;209:1937-52 pubmed publisher
    ..Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice...
  9. von Karstedt S, Conti A, Nobis M, Montinaro A, Hartwig T, Lemke J, et al. Cancer cell-autonomous TRAIL-R signaling promotes KRAS-driven cancer progression, invasion, and metastasis. Cancer Cell. 2015;27:561-73 pubmed publisher
    ..Consistent with this, high TRAIL-R2 expression correlates with invasion of human PDAC into lymph vessels and with shortened metastasis-free survival of KRAS-mutated colorectal cancer patients. ..
  10. Finnberg N, Klein Szanto A, El Deiry W. TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis. J Clin Invest. 2008;118:111-23 pubmed
    ..Thus TRAIL-R may function as an inflammation and tumor suppressor in multiple tissues in vivo. ..
  11. Al Kuhlani M, Rothschild J, Rothchild J, Pal S, de la Maza L, Ouburg S, et al. TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates long-term sequelae resulting from Chlamydia trachomatis infections in humans. PLoS ONE. 2014;9:e93939 pubmed publisher
    ..This is the first evidence that human TRAIL-R1 is a negative regulator of inflammation and plays a role in modulating Chlamydia pathogenesis. ..
  12. Takahashi K, Takeda K, Saiki I, Irimura T, Hayakawa Y. Functional roles of tumor necrosis factor-related apoptosis-inducing ligand-DR5 interaction in B16F10 cells by activating the nuclear factor-?B pathway to induce metastatic potential. Cancer Sci. 2013;104:558-62 pubmed publisher
    ..nuclear factor-?B (NF?B)-luciferase reporter gene, we found that TRAIL can activate NF?B through its death receptor DR5 in B16F10 cells...
  13. Yue H, Diehl G, Winoto A. Loss of TRAIL-R does not affect thymic or intestinal tumor development in p53 and adenomatous polyposis coli mutant mice. Cell Death Differ. 2005;12:94-7 pubmed
  14. McKee C, Ye Y, Richburg J. Testicular germ cell sensitivity to TRAIL-induced apoptosis is dependent upon p53 expression and is synergistically enhanced by DR5 agonistic antibody treatment. Apoptosis. 2006;11:2237-50 pubmed
    The ability of the TRAIL/DR5 signaling pathway to induce apoptosis has generally been limited to tumor cells. Here we report that in primary testis explants, addition of TRAIL (0...
  15. Grigaravicius P, Kaminska E, Hübner C, McKinnon P, von Deimling A, Frappart P. Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain. Cell Death Differ. 2016;23:454-68 pubmed publisher
    ..Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy. ..
  16. Wilson N, Yang A, Yang B, Couto S, Stern H, Gogineni A, et al. Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth. Cancer Cell. 2012;22:80-90 pubmed publisher
    The proapoptotic death receptor DR5 has been studied extensively in cancer cells, but its action in the tumor microenvironment is not well defined. Here, we uncover a role for DR5 signaling in tumor endothelial cells (ECs)...
  17. Thomas L, Henson A, Reed J, Salsbury F, Thorburn A. Direct binding of Fas-associated death domain (FADD) to the tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 is regulated by the death effector domain of FADD. J Biol Chem. 2004;279:32780-5 pubmed
    ..Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signals apoptosis through two receptors, DR4 and DR5. Although there is much interest in TRAIL, the mechanism by which FADD is recruited to the TRAIL receptors is not ..
  18. Riley J, Heeley J, Wyman A, Schlichting E, Moley K. TRAIL and KILLER are expressed and induce apoptosis in the murine preimplantation embryo. Biol Reprod. 2004;71:871-7 pubmed
    ..TRAIL receptor (murine KILLER [MK]) has been identified in mice, and it is a homologue of human Death Receptor 5. Whereas the expression of other death receptors, such as Fas and TNF receptor 1 have been documented in ..
  19. Finnberg N, Gokare P, Navaraj A, Lang Kuhs K, Cerniglia G, Yagita H, et al. Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity. Cancer Res. 2016;76:700-12 pubmed publisher
    ..with a functional DNA damage response (DDR) upregulate the expression of death-inducing receptor DR5/TRAILR2/TNFRSF10B in a p53-dependent manner that sensitizes them to treatment with DR5 agonists...
  20. Lu M, Lawrence D, Marsters S, Acosta Alvear D, Kimmig P, Mendez A, et al. Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis. Science. 2014;345:98-101 pubmed publisher
    ..we report that unmitigated ER stress promoted apoptosis through cell-autonomous, UPR-controlled activation of death receptor 5 (DR5)...
  21. Yu X, Li L, Li Q, Zang X, Liu Z. TRAIL and DR5 promote thyroid follicular cell apoptosis in iodine excess-induced experimental autoimmune thyroiditis in NOD mice. Biol Trace Elem Res. 2011;143:1064-76 pubmed publisher
    ..The expression of TRAIL and its death receptor DR5 was detected by immunofluorescence staining...
  22. Grosse Wilde A, Voloshanenko O, Bailey S, Longton G, Schaefer U, Csernok A, et al. TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development. J Clin Invest. 2008;118:100-10 pubmed
    ..Hence, treatment of cancer patients with agonists of the apoptosis-inducing receptors for TRAIL may prove useful in reducing the incidence of metastasis. ..
  23. Abbas H, Maccio D, Coskun S, Jackson J, Hazen A, SILLS T, et al. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell. 2010;7:606-17 pubmed publisher
    ..p16 was also stabilized because of ROS, and its loss increased cell cycling and partially rescued hematopoiesis and survival. Thus, Mdm2 is required to control ROS-induced p53 levels for sustainable hematopoiesis. ..
  24. Iyori M, Zhang T, Pantel H, Gagne B, Sentman C. TRAIL/DR5 plays a critical role in NK cell-mediated negative regulation of dendritic cell cross-priming of T cells. J Immunol. 2011;187:3087-95 pubmed publisher
    ..In this study, enhanced Ag presentation was observed in draining lymph nodes in TRAIL(-/-) and DR5(-/-) mice compared with that of wild-type mice...
  25. Cardile V, Musumeci G, Sicurezza E, Caggia S, Rusu M, Leonardi R, et al. Expression of TRAIL and its receptors DR5 and DcR2 in orthodontic tooth movement. Histol Histopathol. 2013;28:933-40 pubmed publisher
    ..Expression of TRAIL and its receptors DR5 and DcR2 was examined in osteoclast-like cells to analyze their effects on cell lifespan and to explore their role ..
  26. Zhu J, Chen L, Shi J, Liu S, Liu Y, Zheng D. TRAIL receptor deficiency sensitizes mice to dextran sodium sulphate-induced colitis and colitis-associated carcinogenesis. Immunology. 2014;141:211-21 pubmed publisher
    ..These data suggest that TRAIL-R plays a protective role in chemical-induced colon injury and negatively regulates mucosal immune responses. ..
  27. Guicciardi M, Krishnan A, Bronk S, Hirsova P, Griffith T, Gores G. Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice. Cell Death Dis. 2017;8:e2535 pubmed publisher
    ..Therefore, downregulation of cIAPs in PSC cholangiocytes may contribute to the development of the disease. Our results also indicate that inhibition of TRAIL signaling pathways may be beneficial in the treatment of PSC. ..
  28. Thon L, Mathieu S, Kabelitz D, Adam D. The murine TRAIL receptor signals caspase-independent cell death through ceramide. Exp Cell Res. 2006;312:3808-21 pubmed
  29. Matte Martone C, Venkatesan S, Tan H, Athanasiadis I, Chang J, Pavisic J, et al. Graft-versus-leukemia (GVL) against mouse blast-crisis chronic myelogenous leukemia (BC-CML) and chronic-phase chronic myelogenous leukemia (CP-CML): shared mechanisms of T cell killing, but programmed death ligands render CP-CML and not BC-CML GVL r. J Immunol. 2011;187:1653-63 pubmed publisher
    ..Thus, mBC-CML cells have cell-intrinsic mechanisms, distinct from mCP-CML cells, which protect them from T cell killing. ..
  30. Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber S, et al. Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. J Biol Chem. 2004;279:24813-25 pubmed
    ..Thus Tim50 is important for both mitochondrial function and early neuronal development. ..
  31. Neumann S, Bidon T, Branschädel M, Krippner Heidenreich A, Scheurich P, Doszczak M. The transmembrane domains of TNF-related apoptosis-inducing ligand (TRAIL) receptors 1 and 2 co-regulate apoptotic signaling capacity. PLoS ONE. 2012;7:e42526 pubmed publisher that exerts its apoptotic activity in human cells by binding to two transmembrane receptors, TRAILR1 and TRAILR2. In cells co-expressing both receptors the particular contribution of either protein to the overall cellular ..
  32. Giacomini A, Righi M, Cleris L, Locatelli S, Mitola S, Daidone M, et al. Induction of death receptor 5 expression in tumor vasculature by perifosine restores the vascular disruption activity of TRAIL-expressing CD34(+) cells. Angiogenesis. 2013;16:707-22 pubmed publisher
    The proapoptotic death receptor 5 (DR5) expressed by tumor associated endothelial cells (TECs) mediates vascular disrupting effects of human CD34(+) cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-..
  33. Niu Y, Li Y, Zang J, Huang H, Deng J, Cui Z, et al. Death receptor 5 and neuroproliferation. Cell Mol Neurobiol. 2012;32:255-65 pubmed publisher
    ..apoptosis upon binding to its death domain-containing transmembrane receptors, death receptors 4 and 5 (DR4, DR5)...
  34. Barkic M, Crnomarković S, Grabusic K, Bogetić I, Panic L, Tamarut S, et al. The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival. Mol Cell Biol. 2009;29:2489-504 pubmed publisher
    ..Our results imply that activation of a p53-dependent checkpoint mechanism in response to various ribosomal protein deficiencies might also play a role in the pathogenesis of congenital malformations in humans. ..
  35. Ehlken H, Krishna Subramanian S, Ochoa Callejero L, Kondylis V, Nadi N, Straub B, et al. Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout. Cell Death Differ. 2014;21:1721-32 pubmed publisher
  36. Kao S, Soares V, Kristiansen A, Stankovic K. Activation of TRAIL-DR5 pathway promotes sensorineural degeneration in the inner ear. Aging Cell. 2016;15:301-8 pubmed publisher
    ..for the first time, expression of TNF-related apoptosis-inducing ligand (TRAIL) and its signaling death receptor 5 (DR5) in the murine inner ear and show that exogenous TRAIL can trigger hair cell and neuronal degeneration, ..
  37. Cretney E, Uldrich A, McNab F, Godfrey D, Smyth M. No requirement for TRAIL in intrathymic negative selection. Int Immunol. 2008;20:267-76 pubmed publisher
    ..cellular mediators of negative selection in the thymus, did not constitutively express TRAIL, and TRAIL receptor (DR5) expression was negative or extremely low on thymocytes...
  38. Takeda K, Yamaguchi N, Akiba H, Kojima Y, Hayakawa Y, Tanner J, et al. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. J Exp Med. 2004;199:437-48 pubmed
    ..Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor-..
  39. Li X, McKinstry K, Swain S, Dalton D. IFN-gamma acts directly on activated CD4+ T cells during mycobacterial infection to promote apoptosis by inducing components of the intracellular apoptosis machinery and by inducing extracellular proapoptotic signals. J Immunol. 2007;179:939-49 pubmed
    ..IFN-gamma also up-regulated expression of cell-extrinsic signals of apoptosis, including TRAIL, DR5, and TNFR1...
  40. Yin J, Ni B, Liao W, Gao Y. Hypoxia-induced apoptosis of mouse spermatocytes is mediated by HIF-1? through a death receptor pathway and a mitochondrial pathway. J Cell Physiol. 2018;233:1146-1155 pubmed publisher
    ..In conclusion, our data suggest that the death receptor pathway and mitochondrial pathway, which are likely mediated by HIF-1?, contribute to hypoxia-induced GC-2 cell apoptosis. ..