Secreted protein of the TNF superfamily
LIGHT , also known astumor necrosis factor superfamily member 14 (TNFSF14 ), is a secretedprotein of theTNF superfamily.[ 5] [ 6] [ 7] herpesvirus entry mediator (HVEM), as well asdecoy receptor 3 .
LIGHT stands for "homologous tol ymphotoxin, exhibitsi nducible expression and competes with HSVg lycoprotein D for binding toh erpesvirus entry mediator, a receptor expressed onT lymphocytes". In thecluster of differentiation terminology it is classified asCD258 .
The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). Two alternatively spliced transcript variant encoding distinct isoforms have been reported.[ 6]
This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells,[ 8] [ 9] [ 10] [ 11]
LIGHT has been shown tointeract withTNFRSF14 ,[ 12] [ 13] TNFRSF6B ,[ 12] [ 13] [ 14] BIRC2 ,[ 15] TRAF2 [ 15] TRAF3 .[ 15]
Role in herpes simplex virus [ edit ] Similar to howCD4 is the primary mediating receptor in HIV infection, theHSV glycoprotein (gD ) binds to theHVEM receptor which is demanded by TNFSF14/LIGHT lowering the ability for LIGHT to activate theNFκB pathway. NFκB is a survival factor helping to inhibit apoptosis which triggers a pathway inhibitingcaspase 8 . When gD from HSV binds to HVEM, LIGHT is non-competitively inhibited from binding, encouraging apoptosis in the infected cell.[ 7]
^a b c GRCh38: Ensembl release 89: ENSG00000125735 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000005824 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ Mauri DN, Ebner R, Montgomery RI, Kochel KD, Cheung TC, Yu GL, et al. (January 1998)."LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator" .Immunity .8 (1):21– 30.doi :10.1016/S1074-7613(00)80455-0 PMID 9462508 . ^a b "Entrez Gene: TNFSF14 tumor necrosis factor (ligand) superfamily, member 14" .^a b Ware C (2008). "Chapter 25: TNF-Related Cytokines in Immunity". In Paul W (ed.).Fundamental Immunology 776 –801.ISBN 978-0-7817-6519-0 ^ Tamada K, Shimozaki K, Chapoval AI, Zhai Y, Su J, Chen SF, et al. (April 2000)."LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response" .Journal of Immunology .164 (8):4105– 4110.doi :10.4049/jimmunol.164.8.4105 PMID 10754304 .S2CID 32066617 . ^ Rooney IA, Butrovich KD, Glass AA, Borboroglu S, Benedict CA, Whitbeck JC, et al. (May 2000)."The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells" .The Journal of Biological Chemistry .275 (19):14307– 14315.doi :10.1074/jbc.275.19.14307 PMID 10799510 . ^ He B, Jabouille A, Steri V, Johansson-Percival A, Michael IP, Kotamraju VR, et al. (June 2018)."Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules" .The Journal of Pathology .245 (2):209– 221.doi :10.1002/path.5080 .PMC 6737176 PMID 29603739 . ^ Matsui H, Hikichi Y, Tsuji I, Yamada T, Shintani Y (December 2002)."LIGHT, a member of the tumor necrosis factor ligand superfamily, prevents tumor necrosis factor-alpha-mediated human primary hepatocyte apoptosis, but not Fas-mediated apoptosis" .The Journal of Biological Chemistry .277 (51):50054– 50061.doi :10.1074/jbc.M206562200 PMID 12393901 . ^a b Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, et al. (June 2001)."Modulation of T-cell responses to alloantigens by TR6/DcR3" .The Journal of Clinical Investigation .107 (11):1459– 1468.doi :10.1172/JCI12159 .PMC 209323 PMID 11390428 . ^a b Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (May 1999)."A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis" .The Journal of Biological Chemistry .274 (20):13733– 13736.doi :10.1074/jbc.274.20.13733 PMID 10318773 . ^ Hsu TL, Chang YC, Chen SJ, Liu YJ, Chiu AW, Chio CC, et al. (May 2002)."Modulation of dendritic cell differentiation and maturation by decoy receptor 3" .Journal of Immunology .168 (10):4846– 4853.doi :10.4049/jimmunol.168.10.4846 PMID 11994433 . ^a b c Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin LL (April 2003)."Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis" .The Journal of Biological Chemistry .278 (16):14363– 14369.Bibcode :2003JBiCh.27814363K .doi :10.1074/jbc.M208672200 PMID 12571250 . Yang D, Zhai Y, Zhang M (2003). "LIGHT, a new member of the TNF superfamily".Journal of Biological Regulators and Homeostatic Agents .16 (3):206– 210.PMID 12456019 . Bénichou S, Benmerah A (January 2003)."[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]" .Médecine/Sciences .19 (1):100– 106.doi :10.1051/medsci/2003191100 PMID 12836198 . Anderson JL, Hope TJ (April 2004). "HIV accessory proteins and surviving the host cell".Current HIV/AIDS Reports .1 (1):47– 53.doi :10.1007/s11904-004-0007-x .PMID 16091223 .S2CID 34731265 . Marsters SA, Sheridan JP, Pitti RM, Brush J, Goddard A, Ashkenazi A (April 1998)."Identification of a ligand for the death-domain-containing receptor Apo3" .Current Biology .8 (9):525– 528.Bibcode :1998CBio....8..525M .doi :10.1016/S0960-9822(98)70204-0 PMID 9560343 .S2CID 14953579 . Zhai Y, Guo R, Hsu TL, Yu GL, Ni J, Kwon BS, et al. (September 1998)."LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer" .The Journal of Clinical Investigation .102 (6):1142– 1151.doi :10.1172/JCI3492 .PMC 509097 PMID 9739048 . Harrop JA, McDonnell PC, Brigham-Burke M, Lyn SD, Minton J, Tan KB, et al. (October 1998)."Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth" .The Journal of Biological Chemistry .273 (42):27548– 27556.doi :10.1074/jbc.273.42.27548 PMID 9765287 . Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (May 1999)."A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis" .The Journal of Biological Chemistry .274 (20):13733– 13736.doi :10.1074/jbc.274.20.13733 PMID 10318773 . Rooney IA, Butrovich KD, Glass AA, Borboroglu S, Benedict CA, Whitbeck JC, et al. (May 2000)."The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells" .The Journal of Biological Chemistry .275 (19):14307– 14315.doi :10.1074/jbc.275.19.14307 PMID 10799510 . Lama J, Ware CF (October 2000)."Human immunodeficiency virus type 1 Nef mediates sustained membrane expression of tumor necrosis factor and the related cytokine LIGHT on activated T cells" .Journal of Virology .74 (20):9396– 9402.doi :10.1128/JVI.74.20.9396-9402.2000 .PMC 112368 PMID 11000208 . Morel Y, Schiano de Colella JM, Harrop J, Deen KC, Holmes SD, Wattam TA, et al. (October 2000)."Reciprocal expression of the TNF family receptor herpes virus entry mediator and its ligand LIGHT on activated T cells: LIGHT down-regulates its own receptor" .Journal of Immunology .165 (8):4397– 4404.doi :10.4049/jimmunol.165.8.4397 PMID 11035077 . Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, et al. (June 2001)."Modulation of T-cell responses to alloantigens by TR6/DcR3" .The Journal of Clinical Investigation .107 (11):1459– 1468.doi :10.1172/JCI12159 .PMC 209323 PMID 11390428 . Granger SW, Butrovich KD, Houshmand P, Edwards WR, Ware CF (November 2001)."Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis" .Journal of Immunology .167 (9):5122– 5128.doi :10.4049/jimmunol.167.9.5122 PMID 11673523 . Shaikh RB, Santee S, Granger SW, Butrovich K, Cheung T,Kronenberg M , et al. (December 2001)."Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction" .Journal of Immunology .167 (11):6330– 6337.doi :10.4049/jimmunol.167.11.6330 PMID 11714797 . Bobik A, Kalinina N (December 2001)."Tumor necrosis factor receptor and ligand superfamily family members TNFRSF14 and LIGHT: new players in human atherogenesis" .Arteriosclerosis, Thrombosis, and Vascular Biology .21 (12):1873– 1875.doi :10.1161/atvb.21.12.1873 PMID 11742858 . Wang J, Lo JC, Foster A, Yu P, Chen HM, Wang Y, et al. (December 2001)."The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT" .The Journal of Clinical Investigation .108 (12):1771– 1780.doi :10.1172/JCI13827 .PMC 209470 PMID 11748260 . Hsu TL, Chang YC, Chen SJ, Liu YJ, Chiu AW, Chio CC, et al. (May 2002)."Modulation of dendritic cell differentiation and maturation by decoy receptor 3" .Journal of Immunology .168 (10):4846– 4853.doi :10.4049/jimmunol.168.10.4846 PMID 11994433 . Castellano R, Van Lint C, Peri V, Veithen E, Morel Y, Costello R, et al. (November 2002)."Mechanisms regulating expression of the tumor necrosis factor-related light gene. Role of calcium-signaling pathway in the transcriptional control" .The Journal of Biological Chemistry .277 (45):42841– 42851.doi :10.1074/jbc.M207689200 PMID 12215452 . Matsui H, Hikichi Y, Tsuji I, Yamada T, Shintani Y (December 2002)."LIGHT, a member of the tumor necrosis factor ligand superfamily, prevents tumor necrosis factor-alpha-mediated human primary hepatocyte apoptosis, but not Fas-mediated apoptosis" .The Journal of Biological Chemistry .277 (51):50054– 50061.doi :10.1074/jbc.M206562200 PMID 12393901 . This article incorporates text from theUnited States National Library of Medicine , which is in thepublic domain .
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Chemokine CSF
Interferon
IFNAR (α/β, I) Agonists: Albinterferon Interferon alpha (interferon alfa, IFN-α) Interferon alfa (IFNA1 ,IFNA2 ,IFNA4 ,IFNA5 ,IFNA6 ,IFNA7 ,IFNA8 ,IFNA10 ,IFNA13 ,IFNA14 ,IFNA16 ,IFNA17 ,IFNA21 )Interferon alfa 2a Interferon alfa 2b Interferon alfa n1 Interferon alfacon-1 Interferon alpha-n3 Interferon beta (IFN-β) (IFNB1 ,IFNB3 )Interferon beta 1a Interferon beta 1b Interferon kappa (IFN-ε/κ/τ/ζ, IFNK) Interferon omega (IFN-ω, IFNW1) Peginterferon alfa-2a Peginterferon alfa-2b IFNGR (γ, II) IFNLR (λ, III) See IL-28R (IFNLR)here instead.
Interleukin TGFβ TNF Others
