LIGHT (protein)

LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily.[5][6][7] It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.

TNFSF14
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFSF14, CD258, HVEML, LIGHT, LTg, TR2, TNLG1D, tumor necrosis factor superfamily member 14, TNF superfamily member 14
External IDsOMIM: 604520 MGI: 1355317 HomoloGene: 2822 GeneCards: TNFSF14
Orthologs
SpeciesHumanMouse
Entrez

8740

50930

Ensembl

ENSG00000125735

ENSMUSG00000005824

UniProt

O43557

Q9QYH9

RefSeq (mRNA)

NM_003807
NM_172014
NM_001376887

NM_019418

RefSeq (protein)

NP_003798
NP_742011
NP_001363816

NP_062291

Location (UCSC)Chr 19: 6.66 – 6.67 MbChr 17: 57.5 – 57.5 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 (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] trigger apoptosis of various tumor cells[9] and play a role in vascular normalisation processes.[10] This protein is also reported to prevent tumor necrosis factor alpha-mediated apoptosis in primary hepatocytes.[11]

Interactions

LIGHT has been shown to interact with TNFRSF14,[12][13] TNFRSF6B,[12][13][14] BIRC2,[15] TRAF2[15] and TRAF3.[15]

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.[7]

References

  1. GRCh38: Ensembl release 89: ENSG00000125735 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000005824 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Mauri DN, Ebner R, Montgomery RI, Kochel KD, Cheung TC, Yu GL, Ruben S, Murphy M, Eisenberg RJ, Cohen GH, Spear PG, Ware CF (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.
  6. "Entrez Gene: TNFSF14 tumor necrosis factor (ligand) superfamily, member 14".
  7. Ware, Carl (2008). "Chapter 25: TNF-Related Cytokines in Immunity". In Paul, William (ed.). Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 776–801. ISBN 978-0-7817-6519-0.
  8. Tamada, K; Shimozaki, K; Chapoval, AI; Zhai, Y; Su, J; Chen, SF; Hsieh, SL; Nagata, S; Ni, J; Chen, L (15 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): 4105–10. doi:10.4049/jimmunol.164.8.4105. PMID 10754304. S2CID 32066617.
  9. Rooney, IA; Butrovich, KD; Glass, AA; Borboroglu, S; Benedict, CA; Whitbeck, JC; Cohen, GH; Eisenberg, RJ; Ware, CF (12 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.
  10. He, B; Jabouille, A; Steri, V; Johansson-Percival, A; Michael, IP; Kotamraju, VR; Junckerstorff, R; Nowak, AK; Hamzah, J; Lee, G; Bergers, G; Ganss, R (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.
  11. Matsui, H; Hikichi, Y; Tsuji, I; Yamada, T; Shintani, Y (20 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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): 14363–9. doi:10.1074/jbc.M208672200. PMID 12571250.

Further reading

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