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Gene Review

Tnfrsf10b  -  tumor necrosis factor receptor superfamily...

Mus musculus

Synonyms: DR5, Death receptor 5, Dr5, KILLER, Killer, ...
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Disease relevance of Tnfrsf10b

  • Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases [1].
  • 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-expressing innate immune cells, with no apparent systemic toxicity [1].
  • In the present study, we have generated stable human colon cancer cell lines, in which the function of KILLER/DR5 was ablated using inducible RNA interference [2].
  • Irradiation augmented TRAIL-induced apoptosis in breast cancer cells through up-regulation of DR5, and subsequent activation of caspases-3, -8 and -9 [3].
  • More interestingly, in vivo studies performed in SCID/nonobese diabetic mice transplanted with autologous tumor and transferred with the specific CD4(+) CTL clone in combination with IFN-alpha resulted in an important APO2L/TRAIL-mediated tumor growth inhibition, which was prohibited by soluble TRAIL-R2 [4].

High impact information on Tnfrsf10b

  • These results in mice indicate that a rational monoclonal antibody-based therapy that both causes tumor-cell apoptosis through DR5 and activates T cells may be an effective strategy for cancer immunotherapy in humans [5].
  • Primary fibrosarcomas initiated with the carcinogen 3-methylcholanthrene (MCA), multiorgan metastases and a primary tumor containing as many as 90% tumor cells resistant to DR5-specific monoclonal antibody were rejected without apparent toxicity or induction of autoimmunity [5].
  • Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity [6].
  • Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy [1].
  • Natural Killer (NK) cells can recognize and kill MHC-incompatible normal bone marrow-derived cells [7].

Chemical compound and disease context of Tnfrsf10b


Biological context of Tnfrsf10b

  • MK induces apoptosis in mouse and human cells and inhibits colony growth of NIH3T3 cells [10].
  • In the ileum, colon, and stomach, DR5 deficiency was associated with a subtle phenotype of radiation-induced cell death [11].
  • These results indicate that DR5 has a limited role during embryogenesis and early stages of development but plays an organ-specific role in the response to DNA-damaging stimuli [11].
  • This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5 [12].
  • However, it has not been demonstrated whether they regulate TRAIL-R2 via the promoter region [13].

Anatomical context of Tnfrsf10b

  • We show that DR5 is not expressed in developing embryos but is present in the decidua and chorion early in development [11].
  • When exposed to ionizing radiation, DR5-null tissues exhibit reduced amounts of apoptosis compared to wild-type thymus, spleen, Peyer's patches, and the white matter of the brain [11].
  • DR5-null mouse embryo fibroblasts expressing E1A are resistant to treatment with TRAIL, suggesting that DR5 may be the primary proapoptotic receptor for TRAIL in the mouse [11].
  • At the blastocyst stage, both TRAIL and MK exhibit an apical staining pattern in the trophectoderm cells [14].
  • We first isolated human hepatocytes from patients and showed that the human hepatocytes expressed Fas but no TRAIL death receptor DR4 and little DR5 on the cell surface [15].

Associations of Tnfrsf10b with chemical compounds

  • MK contains an extracellular cysteine-rich domain, a transmembrane domain, and a cytoplasmic death-domain characteristic of Fas, tumor necrosis factor, and human TRAIL receptors [10].
  • Finally, using the TUNEL assay, we demonstrated that MK induces apoptosis in blastocysts sensitized to TRAIL via actinomycin D [14].
  • Inducible silencing of KILLER/DR5 in vivo promotes bioluminescent colon tumor xenograft growth and confers resistance to chemotherapeutic agent 5-fluorouracil [2].
  • IFN-beta up-regulated the expression of TRAIL, while NS-398 increased the expression of TRAIL receptors (especially of death receptor 5) [16].
  • Dox up-regulated the expression of the TRAIL receptor death receptor 5 (DR5) and synergistically enhanced the effect of TRAIL not only against MM cells sensitive to, but also against those resistant to, Dex- or Dox-induced apoptosis [17].

Regulatory relationships of Tnfrsf10b


Other interactions of Tnfrsf10b


Analytical, diagnostic and therapeutic context of Tnfrsf10b

  • Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor [10].
  • Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model [9].
  • Oligomerization of TRAIL-R2 was analyzed by size exclusion chromatography and confocal microscopy, and in vivo efficacy was examined in Colo205 xenograft model.RESULTS: KMTR2 specifically recognized TRAIL-R2 and induced apoptosis with or without cross-linking [22].
  • Immunoprecipitations with the MOABs from 125I-labeled KR3598 cells (Dw5, DR5, MT2, MB3 homozygous, SB2, SB4) demonstrated that at least 4 different subpopulations of class II antigens were present in the lysate [23].
  • Monoclonal antibodies were tested by ELISA for their abilities binding to sDR5 and by flow cytometry for the reactivities to surface DR5 of Jurkat cells [24].


  1. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. Takeda, K., Yamaguchi, N., Akiba, H., Kojima, Y., Hayakawa, Y., Tanner, J.E., Sayers, T.J., Seki, N., Okumura, K., Yagita, H., Smyth, M.J. J. Exp. Med. (2004) [Pubmed]
  2. Inducible silencing of KILLER/DR5 in vivo promotes bioluminescent colon tumor xenograft growth and confers resistance to chemotherapeutic agent 5-fluorouracil. Wang, S., El-Deiry, W.S. Cancer Res. (2004) [Pubmed]
  3. The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice. Shankar, S., Singh, T.R., Chen, X., Thakkar, H., Firnin, J., Srivastava, R.K. Int. J. Oncol. (2004) [Pubmed]
  4. Tumor-infiltrating CD4+ T lymphocytes express APO2 ligand (APO2L)/TRAIL upon specific stimulation with autologous lung carcinoma cells: role of IFN-alpha on APO2L/TRAIL expression and -mediated cytotoxicity. Dorothée, G., Vergnon, I., Menez, J., Echchakir, H., Grunenwald, D., Kubin, M., Chouaib, S., Mami-Chouaib, F. J. Immunol. (2002) [Pubmed]
  5. Eradication of established tumors in mice by a combination antibody-based therapy. Uno, T., Takeda, K., Kojima, Y., Yoshizawa, H., Akiba, H., Mittler, R.S., Gejyo, F., Okumura, K., Yagita, H., Smyth, M.J. Nat. Med. (2006) [Pubmed]
  6. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Ichikawa, K., Liu, W., Zhao, L., Wang, Z., Liu, D., Ohtsuka, T., Zhang, H., Mountz, J.D., Koopman, W.J., Kimberly, R.P., Zhou, T. Nat. Med. (2001) [Pubmed]
  7. An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes. Dissen, E., Ryan, J.C., Seaman, W.E., Fossum, S. J. Exp. Med. (1996) [Pubmed]
  8. Retinoic acid-responsive enhancers located 3' of the Hox A and Hox B homeobox gene clusters. Functional analysis. Langston, A.W., Thompson, J.R., Gudas, L.J. J. Biol. Chem. (1997) [Pubmed]
  9. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Buchsbaum, D.J., Zhou, T., Grizzle, W.E., Oliver, P.G., Hammond, C.J., Zhang, S., Carpenter, M., LoBuglio, A.F. Clin. Cancer Res. (2003) [Pubmed]
  10. Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. Wu, G.S., Burns, T.F., Zhan, Y., Alnemri, E.S., El-Deiry, W.S. Cancer Res. (1999) [Pubmed]
  11. DR5 knockout mice are compromised in radiation-induced apoptosis. Finnberg, N., Gruber, J.J., Fei, P., Rudolph, D., Bric, A., Kim, S.H., Burns, T.F., Ajuha, H., Page, R., Wu, G.S., Chen, Y., McKenna, W.G., Bernhard, E., Lowe, S., Mak, T., El-Deiry, W.S. Mol. Cell. Biol. (2005) [Pubmed]
  12. Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Chinnaiyan, A.M., Prasad, U., Shankar, S., Hamstra, D.A., Shanaiah, M., Chenevert, T.L., Ross, B.D., Rehemtulla, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  13. Promoter of TRAIL-R2 gene. Yoshida, T., Sakai, T. Vitam. Horm. (2004) [Pubmed]
  14. TRAIL and KILLER are expressed and induce apoptosis in the murine preimplantation embryo. Riley, J.K., Heeley, J.M., Wyman, A.H., Schlichting, E.L., Moley, K.H. Biol. Reprod. (2004) [Pubmed]
  15. TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice. Hao, C., Song, J.H., Hsi, B., Lewis, J., Song, D.K., Petruk, K.C., Tyrrell, D.L., Kneteman, N.M. Cancer Res. (2004) [Pubmed]
  16. Cyclooxygenase-2 inhibitor and interferon-beta synergistically induce apoptosis in human hepatoma cells in vitro and in vivo. Nakamoto, N., Higuchi, H., Kanamori, H., Kurita, S., Tada, S., Takaishi, H., Toda, K., Yamada, T., Kumagai, N., Saito, H., Hibi, T. Int. J. Oncol. (2006) [Pubmed]
  17. TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications. Mitsiades, C.S., Treon, S.P., Mitsiades, N., Shima, Y., Richardson, P., Schlossman, R., Hideshima, T., Anderson, K.C. Blood (2001) [Pubmed]
  18. Uterine natural killer cells do not require interleukin-2 for their differentiation or maturation. Croy, B.A., Guimond, M.J., Luross, J., Hahnel, A., Wang, B., van den Heuvel, M. Am. J. Reprod. Immunol. (1997) [Pubmed]
  19. Expression of Fas system-related genes in the testis during development and after toxicant exposure. Boekelheide, K., Lee, J., Shipp, E.B., Richburg, J.H., Li, G. Toxicol. Lett. (1998) [Pubmed]
  20. Interrelationships among brain, endocrine and immune response in ageing and successful ageing: role of metallothionein III isoform. Giacconi, R., Cipriano, C., Muzzioli, M., Gasparini, N., Orlando, F., Mocchegiani, E. Mech. Ageing Dev. (2003) [Pubmed]
  21. Interleukin-12 is not essential for silicosis in mice. Davis, G.S., Pfeiffer, L.M., Hemenway, D.R., Rincon, M. Particle and fibre toxicology [electronic resource]. (2006) [Pubmed]
  22. Enhanced apoptosis and tumor regression induced by a direct agonist antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Motoki, K., Mori, E., Matsumoto, A., Thomas, M., Tomura, T., Humphreys, R., Albert, V., Muto, M., Yoshida, H., Aoki, M., Tamada, T., Kuroki, R., Yoshida, H., Ishida, I., Ware, C.F., Kataoka, S. Clin. Cancer Res. (2005) [Pubmed]
  23. Analysis by sequential immunoprecipitations of the specificities of the monoclonal antibodies TU22,34,35,36,37,39,43,58 and YD1/63.HLK directed against human HLA class II antigens. Ziegler, A., Heinig, J., Müller, C., Götz, H., Thinnes, F.P., Uchańska-Ziegler, B., Wernet, P. Immunobiology (1986) [Pubmed]
  24. Analysis of TRAIL receptor expression using anti-TRAIL death receptor-5 monoclonal antibodies. Ma, Y., Yang, D., Chen, Y. Chin. Med. J. (2003) [Pubmed]
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