The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TNFRSF10D  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: CD264, DCR2, DcR2, Decoy receptor 2, TNF-related apoptosis-inducing ligand receptor 4, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TNFRSF10D


High impact information on TNFRSF10D

  • 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 [6].
  • The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain [6].
  • The human TRAIL-R4 gene has been mapped to chromosome 8p22-21, clustered with three other TRAIL receptors [6].
  • TRAIL-R3 and TRAIL-R4 are receptors that do not transmit an apoptotic signal [7].
  • OCs overexpressed TRAIL decoy receptor DcR2 in the presence of MM T cells and death receptor DR4 in T-cell-depleted cultures [8].

Biological context of TNFRSF10D

  • Upon overexpression, DcR2 did not activate apoptosis or nuclear factor-kappaB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis [9].
  • Androgen withdrawal, by reducing DcR2 expression, might leave the cells vulnerable to cell death signals generated by TRAIL via its functional receptors [10].
  • Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation [4].
  • In cell lines, aberrant methylation of DcR1 was present in 11 of 23 (48%) breast, 10 of 27 (37%) lung and 3 of 7 (43%) MM, whereas aberrant methylation of DcR2 was present in 17 of 23 (74%) breast, 13 of 27 (48%) lung and 5 of 7 (71%) MM [11].
  • Immunohistochemical staining of samples from 10 patients with lung carcinoma suggested that high-level DcR2/TRAIL-R4 expression is a common phenotype observed in patients with non-small cell lung carcinoma [12].

Anatomical context of TNFRSF10D


Associations of TNFRSF10D with chemical compounds


Regulatory relationships of TNFRSF10D


Other interactions of TNFRSF10D

  • While DcR1 prevents the assembly of the death-inducing signaling complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with DR5 within the DISC, where it inhibits initiator caspase activation [19].
  • In addition, DcR2 prevents DR4 recruitment within the DR5 DISC [19].
  • These results suggest that DcR2 functions as an inhibitory Apo2L receptor [9].
  • It has been hypothesized that this difference in TRAIL sensitivity between normal and transformed cells might be due to the expression of the non-death-inducing TRAIL receptors (TRAIL-R) TRAIL-R3 and TRAIL-R4, presumably by competition for limited amounts of TRAIL [20].
  • Down-regulation of FLIP strongly corresponds with down-regulation of CASP8, and this was also found for DCR1 and DCR2 [21].

Analytical, diagnostic and therapeutic context of TNFRSF10D


  1. The TRAIL decoy receptor TRUNDD (DcR2, TRAIL-R4) is induced by adenovirus-p53 overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dependent colon cancer apoptosis. Meng, R.D., McDonald, E.R., Sheikh, M.S., Fornace, A.J., El-Deiry, W.S. Mol. Ther. (2000) [Pubmed]
  2. Progression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosis-inducing ligand. Zhuang, L., Lee, C.S., Scolyer, R.A., McCarthy, S.W., Zhang, X.D., Thompson, J.F., Screaton, G., Hersey, P. Hum. Pathol. (2006) [Pubmed]
  3. Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy. Bouralexis, S., Findlay, D.M., Atkins, G.J., Labrinidis, A., Hay, S., Evdokiou, A. Br. J. Cancer (2003) [Pubmed]
  4. Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. van Noesel, M.M., van Bezouw, S., Salomons, G.S., Voûte, P.A., Pieters, R., Baylin, S.B., Herman, J.G., Versteeg, R. Cancer Res. (2002) [Pubmed]
  5. The synthetic retinoid CD437 selectively induces apoptosis in human lung cancer cells while sparing normal human lung epithelial cells. Sun, S.Y., Yue, P., Chen, X., Hong, W.K., Lotan, R. Cancer Res. (2002) [Pubmed]
  6. 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]
  7. 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]
  8. T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction. Colucci, S., Brunetti, G., Rizzi, R., Zonno, A., Mori, G., Colaianni, G., Del Prete, D., Faccio, R., Liso, A., Capalbo, S., Liso, V., Zallone, A., Grano, M. Blood (2004) [Pubmed]
  9. 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]
  10. TNF-alpha-related apoptosis-inducing ligand decoy receptor DcR2 is targeted by androgen action in the rat ventral prostate. Vindrieux, D., Réveiller, M., Florin, A., Blanchard, C., Ruffion, A., Devonec, M., Benahmed, M., Grataroli, R. J. Cell. Physiol. (2006) [Pubmed]
  11. Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Shivapurkar, N., Toyooka, S., Toyooka, K.O., Reddy, J., Miyajima, K., Suzuki, M., Shigematsu, H., Takahashi, T., Parikh, G., Pass, H.I., Chaudhary, P.M., Gazdar, A.F. Int. J. Cancer (2004) [Pubmed]
  12. Decoy receptor-2 small interfering RNA (siRNA) strategy employing three different siRNA constructs in combination defeats adenovirus-transferred tumor necrosis factor-related apoptosis-inducing ligand resistance in lung cancer cells. Aydin, C., Sanlioglu, A.D., Karacay, B., Ozbilim, G., Dertsiz, L., Ozbudak, O., Akdis, C.A., Salih Sanlioglu, S. Hum. Gene Ther. (2007) [Pubmed]
  13. TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. Phillips, T.A., Ni, J., Pan, G., Ruben, S.M., Wei, Y.F., Pace, J.L., Hunt, J.S. J. Immunol. (1999) [Pubmed]
  14. Control of apoptosis signaling by Apo2 ligand. Marsters, S.A., Pitti, R.A., Sheridan, J.P., Ashkenazi, A. Recent Prog. Horm. Res. (1999) [Pubmed]
  15. 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]
  16. In chronic pancreatitis, widespread emergence of TRAIL receptors in epithelia coincides with neoexpression of TRAIL by pancreatic stellate cells of early fibrotic areas. Hasel, C., Dürr, S., Rau, B., Sträter, J., Schmid, R.M., Walczak, H., Bachem, M.G., Möller, P. Lab. Invest. (2003) [Pubmed]
  17. Low-dose UV-radiation sensitizes keratinocytes to TRAIL-induced apoptosis. Qin, J.Z., Bacon, P., Panella, J., Sitailo, L.A., Denning, M.F., Nickoloff, B.J. J. Cell. Physiol. (2004) [Pubmed]
  18. TRAIL/Apo2L ligands induce apoptosis in malignant rhabdoid tumor cell lines. Yoshida, S., Narita, T., Koshida, S., Ohta, S., Takeuchi, Y. Pediatr. Res. (2003) [Pubmed]
  19. Differential Inhibition of TRAIL-Mediated DR5-DISC Formation by Decoy Receptors 1 and 2. Mérino, D., Lalaoui, N., Morizot, A., Schneider, P., Solary, E., Micheau, O. Mol. Cell. Biol. (2006) [Pubmed]
  20. Regulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes. Leverkus, M., Neumann, M., Mengling, T., Rauch, C.T., Bröcker, E.B., Krammer, P.H., Walczak, H. Cancer Res. (2000) [Pubmed]
  21. Clustering of hypermethylated genes in neuroblastoma. van Noesel, M.M., van Bezouw, S., Voûte, P.A., Herman, J.G., Pieters, R., Versteeg, R. Genes Chromosomes Cancer (2003) [Pubmed]
  22. Amiloride augments TRAIL-induced apoptotic death by inhibiting phosphorylation of kinases and phosphatases associated with the P13K-Akt pathway. Kim, K.M., Lee, Y.J. Oncogene (2005) [Pubmed]
  23. Potential for TRAIL as a therapeutic agent in ovarian cancer. Abdollahi, T. Vitam. Horm. (2004) [Pubmed]
  24. Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro. Pettersen, I., Figenschau, Y., Olsen, E., Bakkelund, W., Smedsröd, B., Sveinbjörnsson, B. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  25. Methylation of apoptosis related genes in the pathogenesis and prognosis of prostate cancer. Suzuki, M., Shigematsu, H., Shivapurkar, N., Reddy, J., Miyajima, K., Takahashi, T., Gazdar, A.F., Frenkel, E.P. Cancer Lett. (2006) [Pubmed]
WikiGenes - Universities