Biology:TNFSF12
 Generic protein structure example |
Tumor necrosis factor ligand superfamily member 12 also known as TNF-related weak inducer of apoptosis (TWEAK) is a protein that in humans is encoded by the TNFSF12 gene.[1][2][3]
Function
TWEAK was discovered in 1997.[1] The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. Leukocytes are the main source of TWEAK including human resting and activated monocytes, dendritic cells and natural killer cells.[4] TWEAK can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis.[3]
Clinical significance
Excessive activation of the TWEAK pathway in chronic injury has been described to promote pathological tissue changes including chronic inflammation, fibrosis and angiogenesis.[5] In chronic liver disease, for example, TWEAK expression is enhanced and causes hepatic stellate cells, which are key regulators of liver fibrosis, to proliferate.[6]
References
- ↑ 1.0 1.1 "TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis". The Journal of Biological Chemistry 272 (51): 32401–10. December 1997. doi:10.1074/jbc.272.51.32401. PMID 9405449.
- ↑ "Identification of a ligand for the death-domain-containing receptor Apo3". Current Biology 8 (9): 525–8. April 1998. doi:10.1016/S0960-9822(98)70204-0. PMID 9560343.
- ↑ 3.0 3.1 "Entrez Gene: TNFSF12 tumor necrosis factor (ligand) superfamily, member 12". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8742.
- ↑ "TWEAK attenuates the transition from innate to adaptive immunity" (in en). Cell 123 (5): 931–44. December 2005. doi:10.1016/j.cell.2005.09.022. PMID 16325585.
- ↑ "TWEAK/Fn14 axis: the current paradigm of tissue injury-inducible function in the midst of complexities". Seminars in Immunology. The TNF family - challenges ahead 26 (3): 229–36. June 2014. doi:10.1016/j.smim.2014.02.006. PMID 24636536.
- ↑ "Interaction of TWEAK with Fn14 leads to the progression of fibrotic liver disease by directly modulating hepatic stellate cell proliferation" (in en). The Journal of Pathology 239 (1): 109–21. February 2016. doi:10.1002/path.4707. PMID 26924336.
Further reading
- "TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor". Cytokine & Growth Factor Reviews 14 (3–4): 241–9. 2004. doi:10.1016/S1359-6101(03)00019-4. PMID 12787562.
- "The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity". Frontiers in Bioscience 9 (1–3): 2273–84. September 2004. doi:10.2741/1395. PMID 15353286.
- "TWEAK induces angiogenesis and proliferation of endothelial cells". The Journal of Biological Chemistry 274 (13): 8455–9. March 1999. doi:10.1074/jbc.274.13.8455. PMID 10085077.
- "TRAIL (Apo2 ligand) and TWEAK (Apo3 ligand) mediate CD4+ T cell killing of antigen-presenting macrophages". Journal of Immunology 164 (6): 2897–904. March 2000. doi:10.4049/jimmunol.164.6.2897. PMID 10706675.
- "Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)". FEBS Letters 485 (2–3): 135–41. November 2000. doi:10.1016/S0014-5793(00)02219-5. PMID 11094155.
- "A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis". Immunity 15 (5): 837–46. November 2001. doi:10.1016/S1074-7613(01)00232-1. PMID 11728344.
- "Multiple pathways of TWEAK-induced cell death". Journal of Immunology 168 (2): 734–43. January 2002. doi:10.4049/jimmunol.168.2.734. PMID 11777967.
- "Dual role for TWEAK in angiogenic regulation". Journal of Cell Science 115 (Pt 2): 267–74. January 2002. doi:10.1242/jcs.115.2.267. PMID 11839778.
- "The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells". Journal of Immunology 169 (10): 6020–9. November 2002. doi:10.4049/jimmunol.169.10.6020. PMID 12421989.
- "Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells". Biochemical and Biophysical Research Communications 299 (3): 488–93. December 2002. doi:10.1016/S0006-291X(02)02670-0. PMID 12445828.
- "Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death". Journal of Immunology 170 (1): 341–8. January 2003. doi:10.4049/jimmunol.170.1.341. PMID 12496418.
- "Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome". Nature 427 (6975): 640–5. February 2004. doi:10.1038/nature02320. PMID 14961121.
- "TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages". Circulation Journal 68 (4): 396–9. April 2004. doi:10.1253/circj.68.396. PMID 15056843.
- "Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes". The Journal of Investigative Dermatology 122 (5): 1175–9. May 2004. doi:10.1111/j.0022-202X.2004.22419.x. PMID 15140220.
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