Biology:LIGHT (protein)

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Short description: Secreted protein of the TNF superfamily


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily.[1][2][3] 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 (HVEM). Two alternatively spliced transcript variant encoding distinct isoforms have been reported.[2]

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,[4] trigger apoptosis of various tumor cells[5] and play a role in vascular normalisation processes.[6] This protein is also reported to prevent tumor necrosis factor alpha-mediated apoptosis in primary hepatocytes.[7]

Interactions

LIGHT has been shown to interact with TNFRSF14,[8][9] TNFRSF6B,[8][9][10] BIRC2,[11] TRAF2[11] and TRAF3.[11]

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.[3]

References

  1. ↑ "LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator". Immunity 8 (1): 21–30. January 1998. doi:10.1016/S1074-7613(00)80455-0. PMID 9462508. 
  2. ↑ 2.0 2.1 "Entrez Gene: TNFSF14 tumor necrosis factor (ligand) superfamily, member 14". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8740. 
  3. ↑ 3.0 3.1 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 978-0-7817-6519-0. https://archive.org/details/fundamentalimmun00paul_601. 
  4. ↑ Tamada, K; Shimozaki, K; Chapoval, AI; Zhai, Y; Su, J; Chen, SF; Hsieh, SL; Nagata, S et al. (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. 
  5. ↑ Rooney, IA; Butrovich, KD; Glass, AA; Borboroglu, S; Benedict, CA; Whitbeck, JC; Cohen, GH; Eisenberg, RJ et al. (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. 
  6. ↑ He, B; Jabouille, A; Steri, V; Johansson-Percival, A; Michael, IP; Kotamraju, VR; Junckerstorff, R; Nowak, AK 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. PMID 29603739. 
  7. ↑ 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. 
  8. ↑ 8.0 8.1 "Modulation of T-cell responses to alloantigens by TR6/DcR3". The Journal of Clinical Investigation 107 (11): 1459–68. June 2001. doi:10.1172/JCI12159. PMID 11390428. 
  9. ↑ 9.0 9.1 "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". The Journal of Biological Chemistry 274 (20): 13733–6. May 1999. doi:10.1074/jbc.274.20.13733. PMID 10318773. 
  10. ↑ "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". Journal of Immunology 168 (10): 4846–53. May 2002. doi:10.4049/jimmunol.168.10.4846. PMID 11994433. 
  11. ↑ 11.0 11.1 11.2 "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. April 2003. doi:10.1074/jbc.M208672200. PMID 12571250. 

Further reading

External links

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



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