TNFSF12

TWEAK was discovered in 1997. 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.{{cite journal | vauthors = Maecker H, Varfolomeev E, Kischkel F, Lawrence D, LeBlanc H, Lee W, Hurst S, Danilenko D, Li J, Filvaroff E, Yang B, Daniel D, Ashkenazi A | title = TWEAK attenuates the transition from innate to adaptive immunity | language = en | journal = Cell | volume = 123 | issue = 5 | pages = 931–44 | date = December 2005 | pmid = 16325585 | doi = 10.1016/j.cell.2005.09.022 | s2cid = 2660454 | doi-access = free }} 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.

Excessive activation of the TWEAK pathway in chronic injury has been described to promote pathological tissue changes including chronic inflammation, fibrosis and angiogenesis.{{cite journal | vauthors = Burkly LC | title = TWEAK/Fn14 axis: the current paradigm of tissue injury-inducible function in the midst of complexities | journal = Seminars in Immunology | volume = 26 | issue = 3 | pages = 229–36 | date = June 2014 | pmid = 24636536 | doi = 10.1016/j.smim.2014.02.006 | series = The TNF family - challenges ahead }} In chronic liver disease, for example, TWEAK expression is enhanced and causes hepatic stellate cells, which are key regulators of liver fibrosis, to proliferate.{{cite journal | vauthors = Wilhelm A, Shepherd EL, Amatucci A, Munir M, Reynolds G, Humphreys E, Resheq Y, Adams DH, Hübscher S, Burkly LC, Weston CJ, Afford SC | title = Interaction of TWEAK with Fn14 leads to the progression of fibrotic liver disease by directly modulating hepatic stellate cell proliferation | language = en | journal = The Journal of Pathology | date = February 2016 | pmid = 26924336 | doi = 10.1002/path.4707 | volume=239 | issue = 1 | pages=109–21| pmc = 4949530 }}

{{clear}}

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Wiley SR, Winkles JA | title = TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor | journal = Cytokine & Growth Factor Reviews | volume = 14 | issue = 3–4 | pages = 241–9 | year = 2004 | pmid = 12787562 | doi = 10.1016/S1359-6101(03)00019-4 }}
• {{cite journal | vauthors = Campbell S, Michaelson J, Burkly L, Putterman C | title = The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity | journal = Frontiers in Bioscience | volume = 9 | issue = 1–3| pages = 2273–84 | date = September 2004 | pmid = 15353286 | doi = 10.2741/1395 | doi-access = free }}
• {{cite journal | vauthors = Lynch CN, Wang YC, Lund JK, Chen YW, Leal JA, Wiley SR | title = TWEAK induces angiogenesis and proliferation of endothelial cells | journal = The Journal of Biological Chemistry | volume = 274 | issue = 13 | pages = 8455–9 | date = March 1999 | pmid = 10085077 | doi = 10.1074/jbc.274.13.8455 | doi-access = free }}
• {{cite journal | vauthors = Kaplan MJ, Ray D, Mo RR, Yung RL, Richardson BC | title = TRAIL (Apo2 ligand) and TWEAK (Apo3 ligand) mediate CD4+ T cell killing of antigen-presenting macrophages | journal = Journal of Immunology | volume = 164 | issue = 6 | pages = 2897–904 | date = March 2000 | pmid = 10706675 | doi = 10.4049/jimmunol.164.6.2897 | doi-access = free }}
• {{cite journal | vauthors = Kaptein A, Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen MJ, Bodmer JL, Tschopp J, Farrow SN | title = Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3) | journal = FEBS Letters | volume = 485 | issue = 2–3 | pages = 135–41 | date = November 2000 | pmid = 11094155 | doi = 10.1016/S0014-5793(00)02219-5 | s2cid = 38403545 | doi-access = free | bibcode = 2000FEBSL.485..135K }}
• {{cite journal | vauthors = Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, Liu H, Daniel TO, Smith CA, Fanslow WC | title = A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis | journal = Immunity | volume = 15 | issue = 5 | pages = 837–46 | date = November 2001 | pmid = 11728344 | doi = 10.1016/S1074-7613(01)00232-1 | doi-access = free }}
• {{cite journal | vauthors = Nakayama M, Ishidoh K, Kayagaki N, Kojima Y, Yamaguchi N, Nakano H, Kominami E, Okumura K, Yagita H | title = Multiple pathways of TWEAK-induced cell death | journal = Journal of Immunology | volume = 168 | issue = 2 | pages = 734–43 | date = January 2002 | pmid = 11777967 | doi = 10.4049/jimmunol.168.2.734 | doi-access = free }}
• {{cite journal | vauthors = Jakubowski A, Browning B, Lukashev M, Sizing I, Thompson JS, Benjamin CD, Hsu YM, Ambrose C, Zheng TS, Burkly LC | title = Dual role for TWEAK in angiogenic regulation | journal = Journal of Cell Science | volume = 115 | issue = Pt 2 | pages = 267–74 | date = January 2002 | doi = 10.1242/jcs.115.2.267 | pmid = 11839778 }}
• {{cite journal | vauthors = Kaplan MJ, Lewis EE, Shelden EA, Somers E, Pavlic R, McCune WJ, Richardson BC | title = The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells | journal = Journal of Immunology | volume = 169 | issue = 10 | pages = 6020–9 | date = November 2002 | pmid = 12421989 | doi = 10.4049/jimmunol.169.10.6020 | doi-access = free }}
• {{cite journal | vauthors = Harada N, Nakayama M, Nakano H, Fukuchi Y, Yagita H, Okumura K | title = Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells | journal = Biochemical and Biophysical Research Communications | volume = 299 | issue = 3 | pages = 488–93 | date = December 2002 | pmid = 12445828 | doi = 10.1016/S0006-291X(02)02670-0 }}
• {{cite journal | vauthors = Nakayama M, Ishidoh K, Kojima Y, Harada N, Kominami E, Okumura K, Yagita H | title = Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death | journal = Journal of Immunology | volume = 170 | issue = 1 | pages = 341–8 | date = January 2003 | pmid = 12496418 | doi = 10.4049/jimmunol.170.1.341 | doi-access = free }}
• {{cite journal | vauthors = Tian XL, Kadaba R, You SA, Liu M, Timur AA, Yang L, Chen Q, Szafranski P, Rao S, Wu L, Housman DE, DiCorleto PE, Driscoll DJ, Borrow J, Wang Q | title = Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome | journal = Nature | volume = 427 | issue = 6975 | pages = 640–5 | date = February 2004 | pmid = 14961121 | pmc = 1618873 | doi = 10.1038/nature02320 | bibcode = 2004Natur.427..640T }}
• {{cite journal | vauthors = Kim SH, Kang YJ, Kim WJ, Woo DK, Lee Y, Kim DI, Park YB, Kwon BS, Park JE, Lee WH | title = TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages | journal = Circulation Journal | volume = 68 | issue = 4 | pages = 396–9 | date = April 2004 | pmid = 15056843 | doi = 10.1253/circj.68.396 | doi-access = free }}
• {{cite journal | vauthors = Jin L, Nakao A, Nakayama M, Yamaguchi N, Kojima Y, Nakano N, Tsuboi R, Okumura K, Yagita H, Ogawa H | title = Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes | journal = The Journal of Investigative Dermatology | volume = 122 | issue = 5 | pages = 1175–9 | date = May 2004 | pmid = 15140220 | doi = 10.1111/j.0022-202X.2004.22419.x | doi-access = free }}

{{refend}}

{{Cytokine receptor modulators}}

{{protein-stub}}