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Gene Review

TNFSF10  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: APO2L, Apo-2 ligand, Apo-2L, CD253, Protein TRAIL, ...
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Disease relevance of TNFSF10


Psychiatry related information on TNFSF10


High impact information on TNFSF10

  • Most importantly, Smac peptides strongly enhanced the antitumor activity of Apo-2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in an intracranial malignant glioma xenograft model in vivo [11].
  • Treatment of colon tumor cells deficient in DNA mismatch repair with the death-receptor ligand apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selected in vitro or in vivo for refractory subclones with Bax frameshift mutations including deletions at a novel site [12].
  • Here we show that in NB4 acute promyelocytic leukemia cells, retinoids selective for retinoic-acid receptor-alpha induced an autoregulatory circuitry of survival programs followed by expression of the membrane-bound tumor-selective death ligand, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand, also called Apo-2L) [13].
  • Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions [14].
  • TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosis of many transformed cell lines but not of normal tissues, even though its death domain-containing receptor, DR4, is expressed on both cell types [15].

Chemical compound and disease context of TNFSF10


Biological context of TNFSF10


Anatomical context of TNFSF10


Associations of TNFSF10 with chemical compounds


Physical interactions of TNFSF10


Regulatory relationships of TNFSF10


Other interactions of TNFSF10

  • To determine whether Apo2L and DR5 were critical for radiation signaling to apoptosis, we stably expressed a dominant negative DR5delta-receptor in Jurkat cells [21].
  • These findings indicate that up-regulation of DR4 and DR5 protein levels by treatment with paclitaxel enhances subsequent Apo-2L/TRAIL-induced apoptosis of human prostate cancer cells [38].
  • Thus, Apo2L/TRAIL and TNF organize common molecular determinants in distinct signaling complexes to stimulate similar kinase pathways [39].
  • In this study, we show by confocal microscopy that FasL and APO2L/TRAIL are mainly localized in lysosomal-like compartments in these cells [40].
  • Cleavage of X-linked inhibitor of apoptosis following IFN-beta and TRAIL/Apo2L treatment was observed in sensitive WM9, A375, or WM3211 cells but not in resistant WM35 or WM164 cells [22].

Analytical, diagnostic and therapeutic context of TNFSF10

  • We have previously shown that mesothelioma cells, resistant to most treatments, are sensitive to the combination of the death ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL/Apo2L) plus chemotherapy [41].
  • All human melanoma cell lines (assessed by annexin V and TUNEL assays) were resistant to apoptosis induction by TRAIL/Apo2L protein [22].
  • We show also by immunoelectron microscopy that FasL and APO2L/TRAIL are stored inside cytoplasmic compartments approximately 500 nm in diameter, with characteristics of multivesicular bodies [40].
  • Administration of Apo2L/TRAIL (0.3, 1, 3, 10, and 30 mg/kg/day for 7 days via i.p. infusion) to nude mice harboring established intracranial U87 xenografts produced a significant, dose-dependent prolongation of survival versus control animals [42].
  • Immunofluorescence staining demonstrated that Apo2L/TRAIL protein was abundant within the cytoplasm of NHBC and OPG was strongly expressed at the cell surface [43].


  1. Overcoming acquired resistance to TRAIL by chemotherapeutic agents and calpain inhibitor I through distinct mechanisms. Zhu, H., Zhang, L., Huang, X., Davis, J.J., Jacob, D.A., Teraishi, F., Chiao, P., Fang, B. Mol. Ther. (2004) [Pubmed]
  2. Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone deacetylase inhibitors. VanOosten, R.L., Earel, J.K., Griffith, T.S. Cancer Gene Ther. (2006) [Pubmed]
  3. Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Chen, Q., Gong, B., Mahmoud-Ahmed, A.S., Zhou, A., Hsi, E.D., Hussein, M., Almasan, A. Blood (2001) [Pubmed]
  4. NF-kappaB-independent actions of sulfasalazine dissociate the CD95L- and Apo2L/TRAIL-dependent death signaling pathways in human malignant glioma cells. Hermisson, M., Weller, M. Cell Death Differ. (2003) [Pubmed]
  5. Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. Zhang, X.D., Franco, A., Myers, K., Gray, C., Nguyen, T., Hersey, P. Cancer Res. (1999) [Pubmed]
  6. TNF-related apoptosis-inducing ligand (TRAIL) induces neuronal apoptosis in HIV-encephalopathy. Miura, Y., Koyanagi, Y., Mizusawa, H. J. Med. Dent. Sci. (2003) [Pubmed]
  7. Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation. Grimm, M., Yeganehfar, W., Laufer, G., Madl, C., Kramer, L., Eisenhuber, E., Simon, P., Kupilik, N., Schreiner, W., Pacher, R., Bunzel, B., Wolner, E., Grimm, G. Circulation (1996) [Pubmed]
  8. Disturbed frontal regulation of attention in Parkinson's disease. Stam, C.J., Visser, S.L., Op de Coul, A.A., De Sonneville, L.M., Schellens, R.L., Brunia, C.H., de Smet, J.S., Gielen, G. Brain (1993) [Pubmed]
  9. Apraxia in Parkinson's disease, progressive supranuclear palsy, multiple system atrophy and neuroleptic-induced parkinsonism. Leiguarda, R.C., Pramstaller, P.P., Merello, M., Starkstein, S., Lees, A.J., Marsden, C.D. Brain (1997) [Pubmed]
  10. Is impaired set-shifting an endophenotype of anorexia nervosa? Holliday, J., Tchanturia, K., Landau, S., Collier, D., Treasure, J. The American journal of psychiatry. (2005) [Pubmed]
  11. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Fulda, S., Wick, W., Weller, M., Debatin, K.M. Nat. Med. (2002) [Pubmed]
  12. Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. LeBlanc, H., Lawrence, D., Varfolomeev, E., Totpal, K., Morlan, J., Schow, P., Fong, S., Schwall, R., Sinicropi, D., Ashkenazi, A. Nat. Med. (2002) [Pubmed]
  13. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C., Gronemeyer, H. Nat. Med. (2001) [Pubmed]
  14. Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Lawrence, D., Shahrokh, Z., Marsters, S., Achilles, K., Shih, D., Mounho, B., Hillan, K., Totpal, K., DeForge, L., Schow, P., Hooley, J., Sherwood, S., Pai, R., Leung, S., Khan, L., Gliniak, B., Bussiere, J., Smith, C.A., Strom, S.S., Kelley, S., Fox, J.A., Thomas, D., Ashkenazi, A. Nat. Med. (2001) [Pubmed]
  15. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Pan, G., Ni, J., Wei, Y.F., Yu, G., Gentz, R., Dixit, V.M. Science (1997) [Pubmed]
  16. Sensitization of AIDS-Kaposi's sarcoma cells to Apo-2 ligand-induced apoptosis by actinomycin D. Mori, S., Murakami-Mori, K., Nakamura, S., Ashkenazi, A., Bonavida, B. J. Immunol. (1999) [Pubmed]
  17. CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release. Röhn, T.A., Wagenknecht, B., Roth, W., Naumann, U., Gulbins, E., Krammer, P.H., Walczak, H., Weller, M. Oncogene (2001) [Pubmed]
  18. Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L. Kemp, T.J., Ludwig, A.T., Earel, J.K., Moore, J.M., Vanoosten, R.L., Moses, B., Leidal, K., Nauseef, W.M., Griffith, T.S. Blood (2005) [Pubmed]
  19. Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis. Jazirehi, A.R., Ng, C.P., Gan, X.H., Schiller, G., Bonavida, B. Clin. Cancer Res. (2001) [Pubmed]
  20. Molecular determinants of epothilone B derivative (BMS 247550) and Apo-2L/TRAIL-induced apoptosis of human ovarian cancer cells. Griffin, D., Wittmann, S., Guo, F., Nimmanapalli, R., Bali, P., Wang, H.G., Bhalla, K. Gynecol. Oncol. (2003) [Pubmed]
  21. 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]
  22. IFN-beta pretreatment sensitizes human melanoma cells to TRAIL/Apo2 ligand-induced apoptosis. Chawla-Sarkar, M., Leaman, D.W., Jacobs, B.S., Borden, E.C. J. Immunol. (2002) [Pubmed]
  23. Control of apoptosis signaling by Apo2 ligand. Marsters, S.A., Pitti, R.A., Sheridan, J.P., Ashkenazi, A. Recent Prog. Horm. Res. (1999) [Pubmed]
  24. 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]
  25. IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Tecchio, C., Huber, V., Scapini, P., Calzetti, F., Margotto, D., Todeschini, G., Pilla, L., Martinelli, G., Pizzolo, G., Rivoltini, L., Cassatella, M.A. Blood (2004) [Pubmed]
  26. 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]
  27. Sensitization of tumor cells to Apo2 ligand/TRAIL-induced apoptosis by inhibition of casein kinase II. Ravi, R., Bedi, A. Cancer Res. (2002) [Pubmed]
  28. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Marsters, S.A., Sheridan, J.P., Pitti, R.M., Huang, A., Skubatch, M., Baldwin, D., Yuan, J., Gurney, A., Goddard, A.D., Godowski, P., Ashkenazi, A. Curr. Biol. (1997) [Pubmed]
  29. Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Yin, D., Zhou, H., Kumagai, T., Liu, G., Ong, J.M., Black, K.L., Koeffler, H.P. Oncogene (2005) [Pubmed]
  30. A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins. Miyazaki, T., Reed, J.C. Nat. Immunol. (2001) [Pubmed]
  31. 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]
  32. Caspase 8-dependent sensitization of cancer cells to TRAIL-induced apoptosis following reovirus-infection. Clarke, P., Meintzer, S.M., Spalding, A.C., Johnson, G.L., Tyler, K.L. Oncogene (2001) [Pubmed]
  33. Role of osteoprotegerin (OPG) in cancer. Holen, I., Shipman, C.M. Clin. Sci. (2006) [Pubmed]
  34. Lipopolysaccharide induces expression of APO2 ligand/TRAIL in human monocytes and macrophages. Halaas, O., Vik, R., Ashkenazi, A., Espevik, T. Scand. J. Immunol. (2000) [Pubmed]
  35. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Guo, F., Nimmanapalli, R., Paranawithana, S., Wittman, S., Griffin, D., Bali, P., O'Bryan, E., Fumero, C., Wang, H.G., Bhalla, K. Blood (2002) [Pubmed]
  36. Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression. Bosque, A., Pardo, J., Martínez-Lorenzo, M.J., Iturralde, M., Marzo, I., Piñeiro, A., Alava, M.A., Naval, J., Anel, A. J. Leukoc. Biol. (2005) [Pubmed]
  37. Overexpression of BCL2 blocks TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. Sun, S.Y., Yue, P., Zhou, J.Y., Wang, Y., Choi Kim, H.R., Lotan, R., Wu, G.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  38. 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]
  39. Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. Varfolomeev, E., Maecker, H., Sharp, D., Lawrence, D., Renz, M., Vucic, D., Ashkenazi, A. J. Biol. Chem. (2005) [Pubmed]
  40. Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells. Monleón, I., Martínez-Lorenzo, M.J., Monteagudo, L., Lasierra, P., Taulés, M., Iturralde, M., Piñeiro, A., Larrad, L., Alava, M.A., Naval, J., Anel, A. J. Immunol. (2001) [Pubmed]
  41. c-Jun N-terminal kinase contributes to apoptotic synergy induced by tumor necrosis factor-related apoptosis-inducing ligand plus DNA damage in chemoresistant, p53 inactive mesothelioma cells. Vivo, C., Liu, W., Broaddus, V.C. J. Biol. Chem. (2003) [Pubmed]
  42. Direct stimulation of apoptotic signaling by soluble Apo2l/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells. Pollack, I.F., Erff, M., Ashkenazi, A. Clin. Cancer Res. (2001) [Pubmed]
  43. Human osteoblasts are resistant to Apo2L/TRAIL-mediated apoptosis. Atkins, G.J., Bouralexis, S., Evdokiou, A., Hay, S., Labrinidis, A., Zannettino, A.C., Haynes, D.R., Findlay, D.M. Bone (2002) [Pubmed]
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