LIGHT (protein)

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
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LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.

Nomenclature

LIGHT stands for "homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes". In the cluster of differentiation terminology it is classified as CD258.

Function

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 ligand (HVEML). 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, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported.

Interactions

LIGHT has been shown to interact with TNFRSF14, TNFRSF6B, BIRC2, TRAF2 and TRAF3.

Role in herpes simplex virus

Similar to how CD4 is the primary mediating receptor in HIV infection, the HSV glycoprotein (gD) binds to the HVEM receptor which is demanded by TNFSF14/LIGHT lowering the ability for LIGHT to activate the NFκB pathway. NFκB is a survival factor helping to inhibit apoptosis which triggers a pathway inhibiting caspase 8. When gD from HSV binds to HVEM, LIGHT is non-competitively inhibited from binding, encouraging apoptosis in the infected cell.

Further reading

• Yang D, Zhai Y, Zhang M (2003). "LIGHT, a new member of the TNF superfamily". Journal of Biological Regulators and Homeostatic Agents. 16 (3): 206–10. 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]". Medecine Sciences. 19 (1): 100–6. 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.
• 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): 525–8. doi:10.1016/S0960-9822(98)70204-0. PMID 9560343.
• Zhai Y, Guo R, Hsu TL, Yu GL, Ni J, Kwon BS, Jiang GW, Lu J, Tan J, Ugustus M, Carter K, Rojas L, Zhu F, Lincoln C, Endress G, Xing L, Wang S, Oh KO, Gentz R, Ruben S, Lippman ME, Hsieh SL, Yang D (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): 1142–51. doi:10.1172/JCI3492. PMC 509097. PMID 9739048.
• Harrop JA, McDonnell PC, Brigham-Burke M, Lyn SD, Minton J, Tan KB, Dede K, Spampanato J, Silverman C, Hensley P, DiPrinzio R, Emery JG, Deen K, Eichman C, Chabot-Fletcher M, Truneh A, Young PR (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): 27548–56. 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): 13733–6. doi:10.1074/jbc.274.20.13733. PMID 10318773.
• Rooney IA, Butrovich KD, Glass AA, Borboroglu S, Benedict CA, Whitbeck JC, Cohen GH, Eisenberg RJ, Ware CF (May 2000). "The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells". The Journal of Biological Chemistry. 275 (19): 14307–15. 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): 9396–402. 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, Khandekar SS, Truneh A, Sweet RW, Gastaut JA, Olive D, Costello RT (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): 4397–404. doi:10.4049/jimmunol.165.8.4397. PMID 11035077.
• Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho YH, Li Y, Moore PA, Wu J (June 2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". The Journal of Clinical Investigation. 107 (11): 1459–68. 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): 5122–8. doi:10.4049/jimmunol.167.9.5122. PMID 11673523.
• Shaikh RB, Santee S, Granger SW, Butrovich K, Cheung T, Kronenberg M, Cheroutre H, Ware CF (December 2001). "Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction". Journal of Immunology. 167 (11): 6330–7. 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): 1873–5. PMID 11742858.
• Wang J, Lo JC, Foster A, Yu P, Chen HM, Wang Y, Tamada K, Chen L, Fu YX (December 2001). "The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT". The Journal of Clinical Investigation. 108 (12): 1771–80. doi:10.1172/JCI13827. PMC 209470. PMID 11748260.
• Hsu TL, Chang YC, Chen SJ, Liu YJ, Chiu AW, Chio CC, Chen L, Hsieh SL (May 2002). "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". Journal of Immunology. 168 (10): 4846–53. doi:10.4049/jimmunol.168.10.4846. PMID 11994433.
• Castellano R, Van Lint C, Peri V, Veithen E, Morel Y, Costello R, Olive D, Collette Y (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): 42841–51. 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): 50054–61. doi:10.1074/jbc.M206562200. PMID 12393901.

External links

• TNFSF14+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.