Biology:Vascular endothelial growth inhibitor
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Vascular endothelial growth inhibitor (VEGI), also known as TNF-like ligand 1A (TL1A) and TNF superfamily member 15 (TNFSF15), is protein that in humans is encoded by the TNFSF15 gene. VEGI is an anti-angiogenic protein.[1] It belongs to tumor necrosis factor (ligand) superfamily, where it is member 15.[2] It is the sole known ligand for death receptor 3,[3] and it can also be recognized by decoy receptor 3.
Function
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF-alpha and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 (death receptor 3) and TNFRSF6B (decoy receptor 3). It can activate both the NF-κB and MAPK signalling pathways, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. An additional isoform encoded by an alternatively spliced transcript variant has been reported but the sequence of this transcript has not been determined.[2]
Clinical relevance
Several TNFSF15 SNPs have been found to be strongly associated with inflammatory bowel disease.[4][5]
References
- ↑ "A gene network for navigating the literature". Nature Genetics 36 (7): 664. Jul 2004. doi:10.1038/ng0704-664. PMID 15226743.
- ↑ 2.0 2.1 "Entrez Gene: TNFSF15 tumor necrosis factor (ligand) superfamily, member 15". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9966.
- ↑ "On death receptor 3 and its ligands…". Immunology 137 (1): 114–116. Sep 2012. doi:10.1111/j.1365-2567.2012.03606.x. PMID 22612445.
- ↑ "TNFSF15 is an ethnic-specific IBD gene". Inflammatory Bowel Diseases 13 (11): 1333–8. Nov 2007. doi:10.1002/ibd.20223. PMID 17663424.
- ↑ "Association study of TNFSF15 polymorphisms in Japanese patients with inflammatory bowel disease". Gut 55 (10): 1527–8. Oct 2006. doi:10.1136/gut.2006.100297. PMID 16966713.
Further reading
- "Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells". Gene 204 (1–2): 35–46. Dec 1997. doi:10.1016/s0378-1119(97)00509-x. PMID 9434163.
- "VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo". FASEB Journal 13 (1): 181–9. Jan 1999. doi:10.1096/fasebj.13.1.181. PMID 9872942.
- "TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells. Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and caspase-3-like protease". The Journal of Biological Chemistry 274 (3): 1479–86. Jan 1999. doi:10.1074/jbc.274.3.1479. PMID 9880523.
- "VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth". Oncogene 18 (47): 6496–504. Nov 1999. doi:10.1038/sj.onc.1203059. PMID 10597252.
- "Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor". Circulation Research 89 (12): 1161–7. Dec 2001. doi:10.1161/hh2401.101909. PMID 11739281.
- "TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator". Immunity 16 (3): 479–92. Mar 2002. doi:10.1016/S1074-7613(02)00283-2. PMID 11911831.
- "A novel secreted splice variant of vascular endothelial cell growth inhibitor". FASEB Journal 16 (7): 742–4. May 2002. doi:10.1096/fj.01-0757fje. PMID 11923219.
- "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. Oct 2003. doi:10.1074/jbc.M305833200. PMID 12882979.
- "Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease". Journal of Immunology 171 (9): 4868–74. Nov 2003. doi:10.4049/jimmunol.171.9.4868. PMID 14568967.
- "Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation". Clinical Immunology 112 (1): 66–77. Jul 2004. doi:10.1016/j.clim.2004.02.007. PMID 15207783.
- "Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis". Cytokine 29 (5): 229–35. Mar 2005. doi:10.1016/j.cyto.2004.12.001. PMID 15760679.
- "VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth". Clinical Cancer Research 11 (15): 5595–602. Aug 2005. doi:10.1158/1078-0432.CCR-05-0384. PMID 16061878.
- "Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease". Human Molecular Genetics 14 (22): 3499–506. Nov 2005. doi:10.1093/hmg/ddi379. PMID 16221758.
- "Isoform of vascular endothelial cell growth inhibitor (VEGI72-251) increases interleukin-2 production by activation of T lymphocytes". Acta Biochimica et Biophysica Sinica 38 (4): 249–53. Apr 2006. doi:10.1111/j.1745-7270.2006.00155.x. PMID 16604264.
- "The T cell costimulator TL1A is induced by FcgammaR signaling in human monocytes and dendritic cells". Journal of Immunology 178 (7): 4033–8. Apr 2007. doi:10.4049/jimmunol.178.7.4033. PMID 17371957.
- "Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis". Journal of Immunology 178 (11): 7325–33. Jun 2007. doi:10.4049/jimmunol.178.11.7325. PMID 17513783.
- "X-ray crystal structure of TNF ligand family member TL1A at 2.1A". Biochemical and Biophysical Research Communications 364 (1): 1–6. Dec 2007. doi:10.1016/j.bbrc.2007.09.097. PMID 17935696.
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