TL1A is a member of the human tumor necrosis factor (TNF) superfamily also known as VEGI (vascular endothelial growth inhibitor) as it may function as an angiogenesis inhibitor. TL1A is abundantly expressed in endothelial cells, but not in B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha.
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|Synonym:||TNFSF15, VEGI, VEGI192A|
|MW (calculated):||43,569 daltons|
|MW (SDS-PAGE):||46 Kd|
|Abs 0.1% (= 1 mg/ml):||1.213|
TL1A is a member of the human tumor necrosis factor (TNF) superfamily also known as VEGI (vascular endothelial growth inhibitor) as it may function as an angiogenesis inhibitor. TL1A is abundantly expressed in endothelial cells, but not in B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. TL1A is a ligand for receptor DR3 and decoy receptor DR6. It can activate NFκB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells.
An additional isoform encoded by an alternatively spliced transcript variant has been reported. In myeloid cells TL1A activated the transcription factor κB (NF-κB), induced degradation of IκBα, and nuclear translocation of p65 subunit of NF-κB. In addition, TL1A activated c-Jun N-terminal kinase. TL1A inhibited the proliferation of breast carcinoma (MCF-7), epithelial (HeLa), and myeloid (U-937 and ML-1a) tumor cells; and activated caspase-3 leading to PARP cleavage. TL1A -induced cytotoxicity was potentiated by inhibitors of protein synthesis. Interesting, TL1A also induced proliferation of normal human foreskin fibroblast cells.
Amino Acid Sequence
1. VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. Zhai Y., Ni J., Jiang G.-W., Lu J., Xing L., Lincoln C., Carter K.C., Janat F., Kozak D., Xu S., Rojas L., Aggarwal B.B., Ruben S., Li L.-Y., Gentz R., Yu G.-L.
2. FASEB J. 13:181-189 (1999)
3. A novel secreted splice variant of vascular endothelial cell growth inhibitor. Chew L.-J., Pan H., Yu J., Tian S., Huang W.-Q., Zhang J.Y., Pang S., Li L.-Y. FASEB J. 16:742-744 (2002)
4. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Migone T.-S., Zhang J., Luo X., Zhuang L., Chen C., Hu B., Hong J.S., Perry J.W., Chen S.-F., Zhou J.X.H., Cho Y.H., Ullrich S., Kanakaraj P., Carrell J., Boyd E., Olsen H.S., Hu G., Pukac L. expand/collapse author list Wei P. Immunity 16:479-492 (2002)
5. X-ray crystal structure of TNF ligand family member TL1A at 2.1A. Jin T., Guo F., Kim S., Howard A., Zhang Y.-Z. Biochem. Biophys. Res. Commun. 364:1-6 (2007)