Decoy receptor 3 explained

Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis.^{[1] [2] [3]}

Discovery

Dcr3 was identified in 1998 by the search of genes with homology to the TNFR gene superfamily in expressed sequence tag (EST) database.

Structure

The open reading frame of TNFRSF6B encodes 300 amino acids with a 29-residue signal sequence and four tandem cystein-rich repeats. Two transcript variants encoding the same isoform, but differing in the 5' UTR, have been observed for this gene.^[3] Unlike most of the other members of TNFR superfamily, TNFRSF6 is a soluble protein which contains no transmembrane domain.

Function

This gene belongs to the tumor necrosis factor receptor superfamily. It acts as a decoy receptor that competes with death receptors for ligand binding. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death and T cell activation as well as to induce angiogenesis via neutralization of TL1A. Overexpression of this gene has been noted in various tumors e.g. gastrointestinal tract tumors, and it is located in a gene-rich cluster on chromosome 20, with other potentially tumor-related genes.^[3]

Interactions

TNFRSF6B has been shown to interact with:

• TNFSF14^{[2] [4] [5]}
• Fas ligand.^{[1] [2] [5]}

Further reading

• Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Res. . 6 . 3 . 197–205 . 1999 . 10470851 . 10.1093/dnares/6.3.197 . 3 . Kikuno R . Nagase T . Ishikawa K . vanc . Hirosawa . M . Miyajima . N . Tanaka . A . Kotani . H . Nomura . N . Ohara . O . free .
• Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster . Proc. Natl. Acad. Sci. U.S.A. . 97 . 3 . 1230–5 . 2000 . 10655513 . 10.1073/pnas.97.3.1230 . 3 . Bai C . Connolly B . Metzker ML . vanc . Hilliard . CA . Liu . X . Sandig . V . Soderman . A . Galloway . SM . Liu . Q . 15578 . 2000PNAS...97.1230B . free .
• The DNA sequence and comparative analysis of human chromosome 20 . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . 3 . Deloukas P . Matthews LH . Ashurst J . vanc . Burton . J . Gilbert . JG . Jones . M . Stavrides . G . Almeida . JP . Babbage . AK . 2001Natur.414..865D . free .
• TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator . Immunity . 16 . 3 . 479–92 . 2002 . 11911831 . 10.1016/S1074-7613(02)00283-2 . 3 . Migone TS . Zhang J . Luo X . vanc . Zhuang . L . Chen . C . Hu . B . Hong . JS . Perry . JW . Chen . SF . free .
• Modulation of dendritic cell differentiation and maturation by decoy receptor 3 . J. Immunol. . 168 . 10 . 4846–53 . 2002 . 11994433 . 10.4049/jimmunol.168.10.4846. 3 . Hsu TL . Chang YC . Chen SJ . vanc . Liu . YJ . Chiu . AW . Chio . CC . Chen . L . Hsieh . SL . free .
• DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer . Int. J. Cancer . 102 . 3 . 254–7 . 2002 . 12397645 . 10.1002/ijc.10711 . 3 . Mild G . Bachmann F . Boulay JL . vanc . Glatz . K . Laffer . U . Lowy . A . Metzger . U . Reuter . J . Terracciano . L . 23680078 .
• Differential Expression of LIGHT and Its Receptors in Human Placental Villi and Amniochorion Membranes . Am. J. Pathol. . 161 . 6 . 2011–7 . 2003 . 12466117 . 10.1016/S0002-9440(10)64479-3. Gill RM . Ni J . Hunt JS . 1850908.
• A TNF family member LIGHT transduces costimulatory signals into human T cells . J. Immunol. . 169 . 12 . 6813–21 . 2003 . 12471113 . 10.4049/jimmunol.169.12.6813. 3 . Wan X . Zhang J . Luo H . vanc . Shi . G . Kapnik . E . Kim . S . Kanakaraj . P . Wu . J . free .
• Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 3 . Strausberg RL . Feingold EA . Grouse LH . vanc . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 139241 . 2002PNAS...9916899M . free .
• DcR3/TR6 modulates immune cell interactions . J. Cell. Biochem. . 89 . 3 . 603–12 . 2003 . 12761893 . 10.1002/jcb.10523 . 3 . Wan X . Shi G . Semenuk M . vanc . Zhang . J . Wu . J . 39322989 .
• Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma . Int. J. Cancer . 106 . 1 . 17–25 . 2003 . 12794752 . 10.1002/ijc.11170 . 3 . Tsuji S . Hosotani R . Yonehara S . vanc . Masui . T . Tulachan . SS . Nakajima . S . Kobayashi . H . Koizumi . M . Toyoda . E . 2433/148465 . 34900944 . free .
• The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 3 . Clark HF . Gurney AL . Abaya E . vanc . Baker . K . Baldwin . D . Brush . J . Chen . J . Chow . B . Chui . C . 403697 .
• Death decoy receptor TR6/DcR3 inhibits T cell chemotaxis in vitro and in vivo . J. Immunol. . 171 . 7 . 3407–14 . 2004 . 14500635 . 10.4049/jimmunol.171.7.3407. Shi G . Wu Y . Zhang J . Wu J . free .
• Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication . J. Leukoc. Biol. . 75 . 2 . 293–306 . 2004 . 14634066 . 10.1189/jlb.0303119 . 3 . Wu SF . Liu TM . Lin YC . vanc . Sytwu . HK . Juan . HF . Chen . ST . Shen . KL . Hsi . SC . Hsieh . SL . 14226200 . free .
• Modulation of macrophage differentiation and activation by decoy receptor 3 . J. Leukoc. Biol. . 75 . 3 . 486–94 . 2004 . 14657214 . 10.1189/jlb.0903448 . 3 . Chang YC . Hsu TL . Lin HH . vanc . Chio . CC . Chiu . AW . Chen . NJ . Lin . CH . Hsieh . SL . 31939119 . free .
• Selective Induction of Tumor Necrosis Receptor Factor 6/Decoy Receptor 3 Release by Bacterial Antigens in Human Monocytes and Myeloid Dendritic Cells . Infect. Immun. . 72 . 1 . 89–93 . 2004 . 14688085 . 10.1128/IAI.72.1.89-93.2004 . 3 . Kim S . McAuliffe WJ . Zaritskaya LS . vanc . Moore . PA . Zhang . L . Nardelli . B . 343977 .
• Enhanced adhesion of monocytes via reverse signaling triggered by decoy receptor 3 . Exp. Cell Res. . 292 . 2 . 241–51 . 2004 . 14697332 . 10.1016/j.yexcr.2003.09.019 . 3 . Hsu MJ . Lin WW . Tsao WC . vanc . Chang . YC . Hsu . TL . Chiu . AW . Chio . CC . Hsieh . SL .
• Soluble Receptor (DcR3) and Cellular Inhibitor of Apoptosis-2 (cIAP-2) Protect Human Cytotrophoblast Cells Against LIGHT-Mediated Apoptosis . Am. J. Pathol. . 165 . 1 . 309–17 . 2004 . 15215185 . 10.1016/S0002-9440(10)63298-1. Gill RM . Hunt JS . 1618528 .

External links

• GeneReviews/NCBI/NIH/UW entry on Autoimmune Lymphoproliferative Syndrome

Notes and References

1. Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A . Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer . Nature . 396 . 6712 . 699–703 . Jan 1999 . 9872321 . 10.1038/25387 . 4427455 .
2. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS . A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis . J Biol Chem . 274 . 20 . 13733–6 . Jun 1999 . 10318773 . 10.1074/jbc.274.20.13733 . free .
3. Web site: Entrez Gene: TNFRSF6B tumor necrosis factor receptor superfamily, member 6b, decoy.
4. Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho YH, Li Y, Moore PA, Wu J . Modulation of T-cell responses to alloantigens by TR6/DcR3 . J. Clin. Invest. . 107 . 11 . 1459–68 . June 2001 . 11390428 . 209323 . 10.1172/JCI12159 .
5. Hsu TL, Chang YC, Chen SJ, Liu YJ, Chiu AW, Chio CC, Chen L, Hsieh SL . Modulation of dendritic cell differentiation and maturation by decoy receptor 3 . J. Immunol. . 168 . 10 . 4846–53 . May 2002 . 11994433 . 10.4049/jimmunol.168.10.4846. free .