From Wikipedia, the free encyclopedia
Secreted protein of the TNF superfamily
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 .
Nomenclature
LIGHT stands for "homologous to l ymphotoxin, exhibits i nducible expression and competes with HSV g lycoprotein D for binding to h erpesvirus 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
^
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, 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 .
^
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 (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp.
776 –801.
ISBN
978-0-7817-6519-0 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^
a
b 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 .
^
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): 13733–6.
doi :
10.1074/jbc.274.20.13733 .
PMID
10318773 .
^ 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 .
^
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): 14363–9.
doi :
10.1074/jbc.M208672200 .
PMID
12571250 .
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]" . Médecine/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 .
S2CID
34731265 .
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.
doi :
10.1161/atvb.21.12.1873 .
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
This article incorporates text from the
United States National Library of Medicine , which is in the
public 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