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Gene Review

TNFRSF10C  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: Antagonist decoy receptor for TRAIL/Apo-2L, CD263, DCR1, DCR1-TNFR, DcR1, ...
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Disease relevance of TNFRSF10C


Psychiatry related information on TNFRSF10C

  • The D21S55 region or Down's Syndrome Chromosome Region 1 (DCR1) (1/20 of the long arm), on 21q22.2-21q22.3 proximal, is involved in four cardinal features of the disease: mental retardation, growth retardation, muscular hypotonia and joint hyperlaxity, and in eight of the 18 more common morphological anomalies of the face, hands and feet [6].

High impact information on TNFRSF10C

  • At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs) [7].
  • The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans [7].
  • Decoy receptor springs to life and eases fibrosis [8].
  • Ectopic expression of TRID protected mammalian cells from TRAIL-induced apoptosis, which is consistent with a protective role [9].
  • TRID transcripts were detected in many normal human tissues but not in most cancer cell lines examined [9].

Chemical compound and disease context of TNFRSF10C


Biological context of TNFRSF10C


Anatomical context of TNFRSF10C

  • For DcR1 and DcR2, we found dense hypermethylation in 9 (69%) of 13 and 9 (90%) of 10 of nonexpressing cell lines, respectively [1].
  • Although all four lines contained mRNA encoding the apoptosis-inducing DR5 receptor, only trophoblast cells contained mRNA encoding the DcR1 decoy receptor and only macrophages contained DcR2 decoy receptor transcripts [13].
  • Using primary gastrointestinal tract (GIT) tumors and their matching normal tissue, we also demonstrate for the first time that TRID expression is enhanced in primary tumors of the GIT [12].
  • TRID has been shown to be overexpressed in normal human tissues but not in malignantly transformed cell lines [12].
  • The mRNAs for DcR1 and DcR2 are expressed in multiple normal tissues but in few tumor cell lines [14].

Associations of TNFRSF10C with chemical compounds


Physical interactions of TNFRSF10C


Regulatory relationships of TNFRSF10C

  • Consistent with these results, exogenous wild-type p53 also upregulates the expression of endogenous TRID in p53-null cells [12].
  • 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 [20].
  • This effect was in accord with our observation that TG predominantly up-regulated both mRNA and protein expression of DR5, as well as DR4 mRNA while down-regulating DcR1 protein in GCT stromal-like tumor cells [20].
  • DCR1 stimulated reporter gene expression in primary lens explants treated with FGF2 linking FGF-signaling with alphaA-crystallin synthesis [21].
  • In contrast, RA SF macrophages expressed TRAIL R3, a decoy receptor (P < 0.01 versus isotype control), but not TRAIL, or TRAIL R1, R2, or R4 [22].

Other interactions of TNFRSF10C

  • The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling [23].
  • Thus, TRAIL receptor-3 may function as an antagonistic decoy receptor to attenuate the cytotoxic effect of TRAIL in most tissues that are TRAIL+, DR4+, and DR5+ [24].
  • By cross-hybridization with DcR1, we have identified a fourth Apo2L receptor, which contains a cytoplasmic region with a truncated death domain [25].
  • The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract [12].
  • In contrast, osteogenic sarcoma cells had low or absent levels of DcR-1 and DcR-2 [26].

Analytical, diagnostic and therapeutic context of TNFRSF10C


  1. 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]
  2. 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]
  3. 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]
  4. 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]
  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. Mapping of the Down syndrome phenotype on chromosome 21 at the molecular level. Sinet, P.M., Théophile, D., Rahmani, Z., Chettouh, Z., Blouin, J.L., Prieur, M., Noel, B., Delabar, J.M. Biomed. Pharmacother. (1994) [Pubmed]
  7. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Tabara, H., Yigit, E., Siomi, H., Mello, C.C. Cell (2002) [Pubmed]
  8. Decoy receptor springs to life and eases fibrosis. MacDonald, T.T. Nat. Med. (2006) [Pubmed]
  9. 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]
  10. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding site. Ruiz de Almodóvar, C., Ruiz-Ruiz, C., Rodríguez, A., Ortiz-Ferrón, G., Redondo, J.M., López-Rivas, A. J. Biol. Chem. (2004) [Pubmed]
  11. 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]
  12. The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Sheikh, M.S., Huang, Y., Fernandez-Salas, E.A., El-Deiry, W.S., Friess, H., Amundson, S., Yin, J., Meltzer, S.J., Holbrook, N.J., Fornace, A.J. Oncogene (1999) [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. Characterization of two receptors for TRAIL. Schneider, P., Bodmer, J.L., Thome, M., Hofmann, K., Holler, N., Tschopp, J. FEBS Lett. (1997) [Pubmed]
  16. TNF-related apoptosis-inducing ligand death pathway-mediated human beta-cell destruction. Ou, D., Metzger, D.L., Wang, X., Huang, J., Pozzilli, P., Tingle, A.J. Diabetologia (2002) [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. Transcription initiation sites and promoter structure of the human TRAIL-R3 gene. Ruiz de Almodóvar, C., López-Rivas, A., Redondo, J.M., Rodríguez, A. FEBS Lett. (2002) [Pubmed]
  19. 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]
  20. 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]
  21. Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. Yang, Y., Stopka, T., Golestaneh, N., Wang, Y., Wu, K., Li, A., Chauhan, B.K., Gao, C.Y., Cveklová, K., Duncan, M.K., Pestell, R.G., Chepelinsky, A.B., Skoultchi, A.I., Cvekl, A. EMBO J. (2006) [Pubmed]
  22. Rheumatoid arthritis synovial fluid macrophages express decreased tumor necrosis factor-related apoptosis-inducing ligand R2 and increased decoy receptor tumor necrosis factor-related apoptosis-inducing ligand R3. Perlman, H., Nguyen, N., Liu, H., Eslick, J., Esser, S., Walsh, K., Moore, T.L., Pope, R.M. Arthritis Rheum. (2003) [Pubmed]
  23. 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]
  24. Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. MacFarlane, M., Ahmad, M., Srinivasula, S.M., Fernandes-Alnemri, T., Cohen, G.M., Alnemri, E.S. J. Biol. Chem. (1997) [Pubmed]
  25. 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]
  26. 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]
  27. 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]
  28. Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells. Sanlioglu, A.D., Dirice, E., Aydin, C., Erin, N., Koksoy, S., Sanlioglu, S. BMC Cancer (2005) [Pubmed]
  29. Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. Eggert, A., Grotzer, M.A., Zuzak, T.J., Wiewrodt, B.R., Ho, R., Ikegaki, N., Brodeur, G.M. Cancer Res. (2001) [Pubmed]
  30. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm. Lonergan, M., Aponso, D., Marvin, K.W., Helliwell, R.J., Sato, T.A., Mitchell, M.D., Chaiwaropongsa, T., Romero, R., Keelan, J.A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  31. Potential for TRAIL as a therapeutic agent in ovarian cancer. Abdollahi, T. Vitam. Horm. (2004) [Pubmed]
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