Death receptor 3
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| Location (UCSC) | Chr 1: 6.46 – 6.47 Mb | Chr 4: 152.2 – 152.2 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a
Function
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. TNFRSF25 is also highly expressed by FoxP3 positive regulatory T lymphocytes. TNFRSF25 is activated by a monogamous ligand, known as TL1A (TNFSF15), which is rapidly upregulated in antigen presenting cells and some endothelial cells following Toll-Like Receptor or Fc receptor activation. This receptor has been shown to signal both through the TRADD adaptor molecule to stimulate NF-kappa B activity or through the FADD adaptor molecule to stimulate caspase activation and regulate cell apoptosis.[6]
Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported, most of which are potentially secreted molecules. The alternative splicing of this gene in B and T cells encounters a programmed change upon T-cell activation, which predominantly produces full-length, membrane bound isoforms, and is thought to be involved in controlling lymphocyte proliferation induced by T-cell activation. Specifically, activation of TNFRSF25 is dependent upon previous engagement of the T cell receptor. Following binding to TL1A, TNFRSF25 signaling increases the sensitivity of T cells to endogenous IL-2 via the IL-2 receptor and enhances T cell proliferation. Because the activation of the receptor is T cell receptor dependent, the activity of TNFRSF25 in vivo is specific to those T cells that are encountering cognate antigen. At rest, and for individuals without underlying autoimmunity, the majority of T cells that regularly encounter cognate antigen are FoxP3+ regulatory T cells. Stimulation of TNFRSF25, in the absence of any other exogenous signals, stimulates profound and highly specific proliferation of FoxP3+ regulatory T cells from their 8-10% of all CD4+ T cells to 35-40% of all CD4+ T cells within 5 days.[9]
Therapeutics
Therapeutic agonists of TNFRSF25 can be used to stimulate
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000215788 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024793 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9052839.
- ^ S2CID 4283742.
- ^ a b "Entrez Gene: TNFRSF25 tumor necrosis factor receptor superfamily, member 25".
- PMID 22612445.
- ^ PMID 20890040.
- PMID 22811539.
- S2CID 19548386.
- PMID 22956587.
Further reading
- Metheny-Barlow LJ, Li LY (2006). "Vascular endothelial growth inhibitor (VEGI), an endogenous negative regulator of angiogenesis". Seminars in Ophthalmology. 21 (1): 49–58. S2CID 41728328.
- Chinnaiyan AM, O'Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J, Dixit VM (Nov 1996). "Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95". Science. 274 (5289): 990–2. S2CID 2348299.
- Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Marsters SA, Sheridan JP, Donahue CJ, Pitti RM, Gray CL, Goddard AD, Bauer KD, Ashkenazi A (Dec 1996). "Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa B". Current Biology. 6 (12): 1669–76. S2CID 16088373.
- Screaton GR, Xu XN, Olsen AL, Cowper AE, Tan R, McMichael AJ, Bell JI (Apr 1997). "LARD: a new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing". Proceedings of the National Academy of Sciences of the United States of America. 94 (9): 4615–9. PMID 9114039.
- Warzocha K, Ribeiro P, Charlot C, Renard N, Coiffier B, Salles G (Jan 1998). "A new death receptor 3 isoform: expression in human lymphoid cell lines and non-Hodgkin's lymphomas". Biochemical and Biophysical Research Communications. 242 (2): 376–9. PMID 9446802.
- Grenet J, Valentine V, Kitson J, Li H, Farrow SN, Kidd VJ (May 1998). "Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human neuroblastoma". Genomics. 49 (3): 385–93. PMID 9615223.
- Jiang Y, Woronicz JD, Liu W, Goeddel DV (Jan 1999). "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains". Science. 283 (5401): 543–6. PMID 9915703.
- Kaptein A, Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen MJ, Bodmer JL, Tschopp J, Farrow SN (Nov 2000). "Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)". FEBS Letters. 485 (2–3): 135–41. PMID 11094155.
- Frankel SK, Van Linden AA, Riches DW (Oct 2001). "Heterogeneity in the phosphorylation of human death receptors by p42(mapk/erk2)". Biochemical and Biophysical Research Communications. 288 (2): 313–20. PMID 11606045.
- Migone TS, Zhang J, Luo X, Zhuang L, Chen C, Hu B, Hong JS, Perry JW, Chen SF, Zhou JX, Cho YH, Ullrich S, Kanakaraj P, Carrell J, Boyd E, Olsen HS, Hu G, Pukac L, Liu D, Ni J, Kim S, Gentz R, Feng P, Moore PA, Ruben SM, Wei P (Mar 2002). "TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator". Immunity. 16 (3): 479–92. PMID 11911831.
- Al-Lamki RS, Wang J, Thiru S, Pritchard NR, Bradley JA, Pober JS, Bradley JR (Aug 2003). "Expression of silencer of death domains and death-receptor-3 in normal human kidney and in rejecting renal transplants". The American Journal of Pathology. 163 (2): 401–11. PMID 12875962.
- Wen L, Zhuang L, Luo X, Wei P (Oct 2003). "TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells". The Journal of Biological Chemistry. 278 (40): 39251–8. PMID 12882979.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biology. 5 (2): R8. PMID 14759258.
- Osawa K, Takami N, Shiozawa K, Hashiramoto A, Shiozawa S (Sep 2004). "Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis". Genes and Immunity. 5 (6): 439–43. S2CID 7357230.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.