Vascular endothelial growth inhibitor

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Tumor necrosis factor (ligand) superfamily, member 15
Protein TNFSF15 PDB 2O0O.png
Rendering based on PDB 2O0O.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TNFSF15 ; TL1; TL1A; VEGI; VEGI192A
External IDs OMIM604052 MGI2180140 HomoloGene3755 GeneCards: TNFSF15 Gene
RNA expression pattern
PBB GE TNFSF15 221085 at tn.png
More reference expression data
Species Human Mouse
Entrez 9966 326623
Ensembl ENSG00000181634 ENSMUSG00000050395
UniProt O95150 Q5UBV8
RefSeq (mRNA) NM_001204344 NM_177371
RefSeq (protein) NP_001191273 NP_796345
Location (UCSC) Chr 9:
117.55 – 117.57 Mb
Chr 4:
63.73 – 63.75 Mb
PubMed search [1] [2]

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic[1] protein. It belongs to tumor necrosis factor (ligand) superfamily, where it is member 15. In humans, it is encoded by the TNFSF15 gene.[2]


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 and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, 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[edit]

Variants in TNFSF15 are strongly associated with inflammatory bowel disease.[3][4]


Further reading[edit]

  • Tan KB, Harrop J, Reddy M, Young P, Terrett J, Emery J, Moore G, Truneh A (December 1997). "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. doi:10.1016/s0378-1119(97)00509-x. PMID 9434163. 
  • Zhai Y, Ni J, Jiang GW, Lu J, Xing L, Lincoln C, Carter KC, Janat F, Kozak D, Xu S, Rojas L, Aggarwal BB, Ruben S, Li LY, Gentz R, Yu GL (January 1999). "VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo". FASEB J. 13 (1): 181–9. PMID 9872942. 
  • Yue TL, Ni J, Romanic AM, Gu JL, Keller P, Wang C, Kumar S, Yu GL, Hart TK, Wang X, Xia Z, DeWolf WE, Feuerstein GZ (January 1999). "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". J. Biol. Chem. 274 (3): 1479–86. doi:10.1074/jbc.274.3.1479. PMID 9880523. 
  • Haridas V, Shrivastava A, Su J, Yu GL, Ni J, Liu D, Chen SF, Ni Y, Ruben SM, Gentz R, Aggarwal BB (November 1999). "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. doi:10.1038/sj.onc.1203059. PMID 10597252. 
  • Yu J, Tian S, Metheny-Barlow L, Chew LJ, Hayes AJ, Pan H, Yu GL, Li LY (December 2001). "Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor". Circ. Res. 89 (12): 1161–7. doi:10.1161/hh2401.101909. PMID 11739281. 
  • 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 (March 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. 
  • Chew LJ, Pan H, Yu J, Tian S, Huang WQ, Zhang JY, Pang S, Li LY (May 2002). "A novel secreted splice variant of vascular endothelial cell growth inhibitor". FASEB J. 16 (7): 742–4. doi:10.1096/fj.01-0757fje. PMID 11923219. 
  • Wen L, Zhuang L, Luo X, Wei P (October 2003). "TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells". J. Biol. Chem. 278 (40): 39251–8. doi:10.1074/jbc.M305833200. PMID 12882979. 
  • Bamias G, Martin C, Marini M, Hoang S, Mishina M, Ross WG, Sachedina MA, Friel CM, Mize J, Bickston SJ, Pizarro TT, Wei P, Cominelli F (November 2003). "Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease". J. Immunol. 171 (9): 4868–74. doi:10.4049/jimmunol.171.9.4868. PMID 14568967. 
  • Prehn JL, Mehdizadeh S, Landers CJ, Luo X, Cha SC, Wei P, Targan SR (July 2004). "Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation". Clin. Immunol. 112 (1): 66–77. doi:10.1016/j.clim.2004.02.007. PMID 15207783. 
  • Kang YJ, Kim WJ, Bae HU, Kim DI, Park YB, Park JE, Kwon BS, Lee WH (2005). "Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis". Cytokine 29 (5): 229–35. doi:10.1016/j.cyto.2004.12.001. PMID 15760679. 
  • Hou W, Medynski D, Wu S, Lin X, Li LY (August 2005). "VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth". Clin. Cancer Res. 11 (15): 5595–602. doi:10.1158/1078-0432.CCR-05-0384. PMID 16061878. 
  • Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, Cardon L, Takazoe M, Tanaka T, Ichimori T, Saito S, Sekine A, Iida A, Takahashi A, Tsunoda T, Lathrop M, Nakamura Y (November 2005). "Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease". Hum. Mol. Genet. 14 (22): 3499–506. doi:10.1093/hmg/ddi379. PMID 16221758. 
  • Yao JJ, Zhang M, Miao XH, Zhao P, Zhu SY, Ding H, Qi ZT (April 2006). "Isoform of vascular endothelial cell growth inhibitor (VEGI72-251) increases interleukin-2 production by activation of T lymphocytes". Acta Biochim. Biophys. Sin. (Shanghai) 38 (4): 249–53. PMID 16604264. 
  • Prehn JL, Thomas LS, Landers CJ, Yu QT, Michelsen KS, Targan SR (April 2007). "The T cell costimulator TL1A is induced by FcgammaR signaling in human monocytes and dendritic cells". J. Immunol. 178 (7): 4033–8. doi:10.4049/jimmunol.178.7.4033. PMID 17371957. 
  • Cassatella MA, Pereira-da-Silva G, da Silva GP, Tinazzi I, Facchetti F, Scapini P, Calzetti F, Tamassia N, Wei P, Nardelli B, Roschke V, Vecchi A, Mantovani A, Bambara LM, Edwards SW, Carletto A (June 2007). "Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis". J. Immunol. 178 (11): 7325–33. doi:10.4049/jimmunol.178.11.7325. PMID 17513783. 
  • Jin T, Guo F, Kim S, Howard A, Zhang YZ (December 2007). "X-ray crystal structure of TNF ligand family member TL1A at 2.1A". Biochem. Biophys. Res. Commun. 364 (1): 1–6. doi:10.1016/j.bbrc.2007.09.097. PMID 17935696.