LIGHT (protein)

TNFSF14
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4EN0, 4J6G, 4KG8, 4KGG, 4KGQ, 4RSU
Identifiers
Aliases	TNFSF14, CD258, HVEML, LIGHT, LTg, TR2, TNLG1D, tumor necrosis factor superfamily member 14
External IDs	MGI: 1355317 HomoloGene: 2822 GeneCards: TNFSF14
Genetically Related Diseases
multiple sclerosis[1]
Gene ontology Molecular function • receptor binding • tumor necrosis factor receptor binding • cytokine activity • cysteine-type endopeptidase inhibitor activity involved in apoptotic process • protein binding Cellular component • extracellular region • cytoplasm • integral component of membrane • extracellular space • membrane • plasma membrane Biological process • T cell costimulation • release of cytoplasmic sequestered NF-kappaB • T cell proliferation • T cell homeostasis • positive regulation of T cell chemotaxis • apoptotic process • tumor necrosis factor-mediated signaling pathway • positive regulation of myoblast fusion • T cell activation • positive regulation of myoblast differentiation • cellular response to mechanical stimulus • immune response • signal transduction • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8740	50930
Ensembl	ENSG00000125735	ENSMUSG00000005824
UniProt	O43557	Q9QYH9
RefSeq (mRNA)	NM_003807 NM_172014	NM_019418
RefSeq (protein)	NP_003798.2 NP_742011.2	NP_062291.1
Location (UCSC)	Chr 19: 6.66 – 6.67 Mb	Chr 17: 57.19 – 57.19 Mb
PubMed search	[2]	[3]
Wikidata

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LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily.^[4][5][6] 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.^[5]

Interactions

LIGHT has been shown to interact with TNFRSF14,^[7][8] TNFRSF6B,^[7][8][9] BIRC2,^[10] TRAF2^[10] and TRAF3.^[10]

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.^[6]

References

1. "Diseases that are genetically associated with TNFSF14 view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Mauri DN, Ebner R, Montgomery RI, Kochel KD, Cheung TC, Yu GL, Ruben S, Murphy M, Eisenberg RJ, Cohen GH, Spear PG, Ware CF (February 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.
5. "Entrez Gene: TNFSF14 tumor necrosis factor (ligand) superfamily, member 14".
6. Ware, Carl (2008). "Chapter 25: TNF-Related Cytokines in Immunity". In Paul, William. Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 776–801. ISBN 0-7817-6519-6.
7. 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". J. Clin. Invest. United States. 107 (11): 1459–68. doi:10.1172/JCI12159. ISSN 0021-9738. PMC 209323. PMID 11390428.
8. Yu, K Y; Kwon B; Ni J; Zhai Y; Ebner R; Kwon B S (May 1999). "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". J. Biol. Chem. UNITED STATES. 274 (20): 13733–6. doi:10.1074/jbc.274.20.13733. ISSN 0021-9258. PMID 10318773.
9. Hsu, Tsui-Ling; Chang Yung-Chi; Chen Siu-Ju; Liu Yong-Jun; Chiu Allen W; Chio Chung-Ching; Chen Lieping; Hsieh Shie-Liang (May 2002). "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". J. Immunol. United States. 168 (10): 4846–53. doi:10.4049/jimmunol.168.10.4846. ISSN 0022-1767. PMID 11994433.
10. Kuai, Jun; Nickbarg Elliott; Wooters Joe; Qiu Yongchang; Wang Jack; Lin Lih-Ling (April 2003). "Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis". J. Biol. Chem. United States. 278 (16): 14363–9. doi:10.1074/jbc.M208672200. ISSN 0021-9258. PMID 12571250.

Further reading

• Yang D, Zhai Y, Zhang M (2003). "LIGHT, a new member of the TNF superfamily". J. Biol. Regul. Homeost. Agents. 16 (3): 206–10. PMID 12456019.
• Bénichou S, Benmerah A (2003). "[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]". Med Sci (Paris). 19 (1): 100–6. doi:10.1051/medsci/2003191100. PMID 12836198.
• Anderson JL, Hope TJ (2005). "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, et al. (1998). "Identification of a ligand for the death-domain-containing receptor Apo3". Curr. Biol. 8 (9): 525–8. doi:10.1016/S0960-9822(98)70204-0. PMID 9560343.
• Zhai Y, Guo R, Hsu TL, et al. (1998). "LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer". J. Clin. Invest. 102 (6): 1142–51. doi:10.1172/JCI3492. PMC 509097. PMID 9739048.
• Harrop JA, McDonnell PC, Brigham-Burke M, et al. (1998). "Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth". J. Biol. Chem. 273 (42): 27548–56. doi:10.1074/jbc.273.42.27548. PMID 9765287.
• Yu KY, Kwon B, Ni J, et al. (1999). "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". J. Biol. Chem. 274 (20): 13733–6. doi:10.1074/jbc.274.20.13733. PMID 10318773.
• Rooney IA, Butrovich KD, Glass AA, et al. (2000). "The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells". J. Biol. Chem. 275 (19): 14307–15. doi:10.1074/jbc.275.19.14307. PMID 10799510.
• Lama J, Ware CF (2000). "Human Immunodeficiency Virus Type 1 Nef Mediates Sustained Membrane Expression of Tumor Necrosis Factor and the Related Cytokine LIGHT on Activated T Cells". J. Virol. 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, et al. (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". J. Immunol. 165 (8): 4397–404. doi:10.4049/jimmunol.165.8.4397. PMID 11035077.
• Zhang J, Salcedo TW, Wan X, et al. (2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". J. Clin. Invest. 107 (11): 1459–68. doi:10.1172/JCI12159. PMC 209323. PMID 11390428.
• Granger SW, Butrovich KD, Houshmand P, et al. (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". J. Immunol. 167 (9): 5122–8. doi:10.4049/jimmunol.167.9.5122. PMID 11673523.
• Shaikh RB, Santee S, Granger SW, et al. (2002). "Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction". J. Immunol. 167 (11): 6330–7. doi:10.4049/jimmunol.167.11.6330. PMID 11714797.
• Bobik A, Kalinina N (2002). "Tumor necrosis factor receptor and ligand superfamily family members TNFRSF14 and LIGHT: new players in human atherogenesis". Arterioscler. Thromb. Vasc. Biol. 21 (12): 1873–5. PMID 11742858.
• Wang J, Lo JC, Foster A, et al. (2002). "The regulation of T cell homeostasis and autoimmunity by T cell–derived LIGHT". J. Clin. Invest. 108 (12): 1771–80. doi:10.1172/JCI13827. PMC 209470. PMID 11748260.
• Hsu TL, Chang YC, Chen SJ, et al. (2002). "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". J. Immunol. 168 (10): 4846–53. doi:10.4049/jimmunol.168.10.4846. PMID 11994433.
• Castellano R, Van Lint C, Peri V, et al. (2003). "Mechanisms regulating expression of the tumor necrosis factor-related light gene. Role of calcium-signaling pathway in the transcriptional control". J. Biol. Chem. 277 (45): 42841–51. doi:10.1074/jbc.M207689200. PMID 12215452.
• Matsui H, Hikichi Y, Tsuji I, et al. (2003). "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". J. Biol. Chem. 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.