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Gene Review

TNFRSF10B  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: CD262, DR5, Death receptor 5, KILLER, KILLER/DR5, ...
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Disease relevance of TNFRSF10B


Psychiatry related information on TNFRSF10B

  • The authors concluded that AIDS-like laboratory alterations are present in clinically unaffected IV drug users; the possible role of DR5 in conditioning different individual susceptibility is considered [5].

High impact information on TNFRSF10B

  • KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene [6].
  • 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 [7].
  • 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 [7].
  • We have studied the molecular basis of HLA-DR polymorphism within such a group which includes the haplotypes DR3, DR5 and DRw6 [8].
  • The receptor designated death receptor 5 (DR5) contained a cytoplasmic death domain and induced apoptosis much like DR4 [9].

Chemical compound and disease context of TNFRSF10B


Biological context of TNFRSF10B


Anatomical context of TNFRSF10B


Associations of TNFRSF10B with chemical compounds


Physical interactions of TNFRSF10B

  • In an in vitro binding assay, the intracellular domains of both TRAIL-R1 and TRAIL-R2 bound FADD: activation of PKC significantly inhibited this interaction suggesting that PKC may be targeting key apical components of death receptor signaling [26].
  • JNK inhibition with SP600125 also blocked binding of Sp1 to the DR5/TRAIL-R2 promoter [27].
  • Moreover, we show that a cellular membrane permeable version of the peptide corresponding to the DR5 binding domain of c-FLIP induces apoptosis in mammalian cells [28].
  • Mutagenesis of the FP330-3' site suggested that either the upstream DR-5 or downstream DR-1 could mediate binding of RAR/RXR [29].
  • Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5 [30].

Regulatory relationships of TNFRSF10B

  • Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells [31].
  • In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis [18].
  • Taken together, our findings suggest that TG is able to sensitize tumor cells of GCT to TRAIL-induced cell death, perhaps in part through up-regulating the death receptor DR5 and down-regulating the decoy receptor DcR1 [32].
  • IFN-alpha pretreatment enhanced TRAIL-induced apoptosis of HuH-7 and Hep3B cells, in which IFN-alpha upregulated the expression of DR5, a death receptor of TRAIL, and downregulated the expression of survivin, which has an antiapoptotic function [33].
  • Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1 [34].

Other interactions of TNFRSF10B

  • Here we show that TRAIL-R1 can associate with TRAIL-R2, suggesting that TRAIL may signal through heteroreceptor signaling complexes [35].
  • FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2 [20].
  • The signaling capacity of TRAIL-R4 is similar to that of TRAIL-R1 and TRAIL-R2 with respect to NF-kappaB activation, but differs in its inability to induce apoptosis [36].
  • On activation, both cell types rapidly expressed TRAIL-R2 and TRAIL-R3, whose expression peaked at day 10 of culture [37].
  • However, unlike other p53-regulated genes, KILLER/DR5 is not regulated following UV irradiation [18].

Analytical, diagnostic and therapeutic context of TNFRSF10B

  • Here we report the identification of a distinct receptor for TRAIL, TRAIL-R2, by ligand-based affinity purification and subsequent molecular cloning [17].
  • On the contrary, DR5 was located on the cell surface in all four sensitive lines tested, being absent only from the cell surface of the resistant line that was also DR5-negative by Western blotting [2].
  • Because these data suggested that sensitivity of ESFTs to TRAIL was mainly based on the presence of DR4/DR5, we investigated the presence of these receptors in 32 ESFT tissue sections by immunohistochemistry [2].
  • Reverse transcriptase-polymerase chain reaction demonstrated tumor necrosis factor-R1, tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-R1/DR4, -R2/DR5, and TRAIL, but not tumor necrosis factor-alpha expression by these cells [38].
  • However, the augmentation of Apo2L/TRAIL effects by chemotherapy was associated with drug-induced up-regulation of death receptors DR4 and DR5 mRNA and protein [39].


  1. TRAIL and its receptors in the colonic epithelium: a putative role in the defense of viral infections. Sträter, J., Walczak, H., Pukrop, T., Von Müller, L., Hasel, C., Kornmann, M., Mertens, T., Möller, P. Gastroenterology (2002) [Pubmed]
  2. Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5. Mitsiades, N., Poulaki, V., Mitsiades, C., Tsokos, M. Cancer Res. (2001) [Pubmed]
  3. Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis. Taimr, P., Higuchi, H., Kocova, E., Rippe, R.A., Friedman, S., Gores, G.J. Hepatology (2003) [Pubmed]
  4. TRAIL-R2 (DR5) mediates apoptosis of synovial fibroblasts in rheumatoid arthritis. Ichikawa, K., Liu, W., Fleck, M., Zhang, H., Zhao, L., Ohtsuka, T., Wang, Z., Liu, D., Mountz, J.D., Ohtsuki, M., Koopman, W.J., Kimberly, R., Zhou, T. J. Immunol. (2003) [Pubmed]
  5. AIDS-like immunologic alterations in clinically unaffected drug users. Fiorini, G., Marinig, C., Riboli, P., Onida, L., Aversa, A.M., Renoldi, P., Marini, U., Gibelli, A. Am. J. Clin. Pathol. (1985) [Pubmed]
  6. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Wu, G.S., Burns, T.F., McDonald, E.R., Jiang, W., Meng, R., Krantz, I.D., Kao, G., Gan, D.D., Zhou, J.Y., Muschel, R., Hamilton, S.R., Spinner, N.B., Markowitz, S., Wu, G., el-Deiry, W.S. Nat. Genet. (1997) [Pubmed]
  7. 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]
  8. Polymorphism of human Ia antigens: gene conversion between two DR beta loci results in a new HLA-D/DR specificity. Gorski, J., Mach, B. Nature (1986) [Pubmed]
  9. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Sheridan, J.P., Marsters, S.A., Pitti, R.M., Gurney, A., Skubatch, M., Baldwin, D., Ramakrishnan, L., Gray, C.L., Baker, K., Wood, W.I., Goddard, A.D., Godowski, P., Ashkenazi, A. Science (1997) [Pubmed]
  10. Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells. Delmas, D., Rébé, C., Micheau, O., Athias, A., Gambert, P., Grazide, S., Laurent, G., Latruffe, N., Solary, E. Oncogene (2004) [Pubmed]
  11. The TRAIL apoptotic pathway mediates proteasome inhibitor induced apoptosis in primary chronic lymphocytic leukemia cells. Kabore, A.F., Sun, J., Hu, X., McCrea, K., Johnston, J.B., Gibson, S.B. Apoptosis (2006) [Pubmed]
  12. Cellular FLICE-Inhibitory Protein Down-regulation Contributes to Celecoxib-Induced Apoptosis in Human Lung Cancer Cells. Liu, X., Yue, P., Sch??nthal, A.H., Khuri, F.R., Sun, S.Y. Cancer Res. (2006) [Pubmed]
  13. c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1, 9-dien-28-oate in human lung cancer cells. Zou, W., Liu, X., Yue, P., Zhou, Z., Sporn, M.B., Lotan, R., Khuri, F.R., Sun, S.Y. Cancer Res. (2004) [Pubmed]
  14. Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells. Matsui, T.A., Sowa, Y., Yoshida, T., Murata, H., Horinaka, M., Wakada, M., Nakanishi, R., Sakabe, T., Kubo, T., Sakai, T. Carcinogenesis (2006) [Pubmed]
  15. 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. Wolf, S., Mertens, D., Pscherer, A., Schroeter, P., Winkler, D., Gröne, H.J., Hofele, C., Hemminki, K., Kumar, R., Steineck, G., Döhner, H., Stilgenbauer, S., Lichter, P. Int. J. Cancer (2006) [Pubmed]
  16. Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Chaudhary, P.M., Eby, M., Jasmin, A., Bookwalter, A., Murray, J., Hood, L. Immunity (1997) [Pubmed]
  17. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. Walczak, H., Degli-Esposti, M.A., Johnson, R.S., Smolak, P.J., Waugh, J.Y., Boiani, N., Timour, M.S., Gerhart, M.J., Schooley, K.A., Smith, C.A., Goodwin, R.G., Rauch, C.T. EMBO J. (1997) [Pubmed]
  18. p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. Sheikh, M.S., Burns, T.F., Huang, Y., Wu, G.S., Amundson, S., Brooks, K.S., Fornace, A.J., el-Deiry, W.S. Cancer Res. (1998) [Pubmed]
  19. Transcriptional response to ionizing radiation in lymphocyte subsets. Mori, M., Benotmane, M.A., Tirone, I., Hooghe-Peters, E.L., Desaintes, C. Cell. Mol. Life Sci. (2005) [Pubmed]
  20. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Sprick, M.R., Weigand, M.A., Rieser, E., Rauch, C.T., Juo, P., Blenis, J., Krammer, P.H., Walczak, H. Immunity (2000) [Pubmed]
  21. Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to tumor necrosis factor-related apoptosis-inducing ligand. Mitsiades, N., Poulaki, V., Tseleni-Balafouta, S., Koutras, D.A., Stamenkovic, I. Cancer Res. (2000) [Pubmed]
  22. Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Gajate, C., Mollinedo, F. Blood (2007) [Pubmed]
  23. Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Singh, T.R., Shankar, S., Chen, X., Asim, M., Srivastava, R.K. Cancer Res. (2003) [Pubmed]
  24. Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. Nimmanapalli, R., Perkins, C.L., Orlando, M., O'Bryan, E., Nguyen, D., Bhalla, K.N. Cancer Res. (2001) [Pubmed]
  25. Apo2 ligand/TNF-related apoptosis-inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells. Gong, B., Almasan, A. Cancer Res. (2000) [Pubmed]
  26. Protein kinase C modulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by targeting the apical events of death receptor signaling. Harper, N., Hughes, M.A., Farrow, S.N., Cohen, G.M., MacFarlane, M. J. Biol. Chem. (2003) [Pubmed]
  27. Bile acids up-regulate death receptor 5/TRAIL-receptor 2 expression via a c-Jun N-terminal kinase-dependent pathway involving Sp1. Higuchi, H., Grambihler, A., Canbay, A., Bronk, S.F., Gores, G.J. J. Biol. Chem. (2004) [Pubmed]
  28. Fas-associated protein with death domain (FADD)-independent recruitment of c-FLIPL to death receptor 5. Jin, T.G., Kurakin, A., Benhaga, N., Abe, K., Mohseni, M., Sandra, F., Song, K., Kay, B.K., Khosravi-Far, R. J. Biol. Chem. (2004) [Pubmed]
  29. Identification of a retinoid receptor response element in the human aldehyde dehydrogenase-2 promoter. Pinaire, J., Chou, W.Y., Morton, M., You, M., Zeng, Y., Cho, W.K., Galli, A., Everett, L., Breen, H., Dumaual, N., Smith, J.R., Crabb, D. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  30. Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Hymowitz, S.G., Christinger, H.W., Fuh, G., Ultsch, M., O'Connell, M., Kelley, R.F., Ashkenazi, A., de Vos, A.M. Mol. Cell (1999) [Pubmed]
  31. Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells. Wen, J., Ramadevi, N., Nguyen, D., Perkins, C., Worthington, E., Bhalla, K. Blood (2000) [Pubmed]
  32. Thapsigargin potentiates TRAIL-induced apoptosis in giant cell tumor of bone. Huang, L., Xu, J., Li, K., Zheng, M.H., Kumta, S.M. Bone (2004) [Pubmed]
  33. Interferon-alpha sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-kappa B inactivation. Shigeno, M., Nakao, K., Ichikawa, T., Suzuki, K., Kawakami, A., Abiru, S., Miyazoe, S., Nakagawa, Y., Ishikawa, H., Hamasaki, K., Nakata, K., Ishii, N., Eguchi, K. Oncogene (2003) [Pubmed]
  34. Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1. Shetty, S., Graham, B.A., Brown, J.G., Hu, X., Vegh-Yarema, N., Harding, G., Paul, J.T., Gibson, S.B. Mol. Cell. Biol. (2005) [Pubmed]
  35. TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Schneider, P., Thome, M., Burns, K., Bodmer, J.L., Hofmann, K., Kataoka, T., Holler, N., Tschopp, J. Immunity (1997) [Pubmed]
  36. The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Degli-Esposti, M.A., Dougall, W.C., Smolak, P.J., Waugh, J.Y., Smith, C.A., Goodwin, R.G. Immunity (1997) [Pubmed]
  37. Activated human NK and CD8+ T cells express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL-mediated cytotoxicity. Mirandola, P., Ponti, C., Gobbi, G., Sponzilli, I., Vaccarezza, M., Cocco, L., Zauli, G., Secchiero, P., Manzoli, F.A., Vitale, M. Blood (2004) [Pubmed]
  38. The bile acid glycochenodeoxycholate induces trail-receptor 2/DR5 expression and apoptosis. Higuchi, H., Bronk, S.F., Takikawa, Y., Werneburg, N., Takimoto, R., El-Deiry, W., Gores, G.J. J. Biol. Chem. (2001) [Pubmed]
  39. Chemotherapeutic agents sensitize osteogenic sarcoma cells, but not normal human bone cells, to Apo2L/TRAIL-induced apoptosis. Evdokiou, A., Bouralexis, S., Atkins, G.J., Chai, F., Hay, S., Clayer, M., Findlay, D.M. Int. J. Cancer (2002) [Pubmed]
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