Lymphotoxin-beta (LT-beta) formerly known as tumor necrosis factor C (TNF-C) is a protein that in humans is encoded by the LTB gene.[5][6][7]
Structure
Lymphotoxin-beta (LTB) is a type II membrane protein belonging to the TNF family. It forms heterotrimers with lymphotoxin-alpha, anchoring it to the cell surface. The predominant complex found on the surface of lymphocytes is the lymphotoxin-alpha 1/beta 2 complex (i.e., one molecule of alpha and two molecules of beta), which serves as the primary ligand for the lymphotoxin-beta receptor. A less common form is the lymphotoxin-alpha 2/beta 1 complex. Additionally, alternative splicing of the LTB gene results in multiple transcript variants encoding different isoforms. Notably, the lymphotoxin-beta isoform b cannot form a complex with lymphotoxin-alpha, indicating it may have functions independent of lymphotoxin-alpha.[7]
Function
LTB plays a critical role in immune system regulation. It is an inducer of the inflammatory response and is essential for the normal development of lymphoid tissues. The membrane-bound lymphotoxin complexes mediate signaling through the lymphotoxin-beta receptor, influencing immune cell differentiation and tissue organization.[7]
Clinical significance
The membrane-bound form of lymphotoxin has been implicated in tumorigenesis. Mice engineered to overexpress LTα or LTβ exhibit increased tumor growth and metastasis in several cancer models. However, earlier studies were limited by the use of mice lacking the entire LTα gene, making it difficult to distinguish the effects of soluble versus membrane-associated lymphotoxins.[8]
Interactions
LTB has been shown to interact with Lymphotoxin alpha.[9][10][11]
References
- ^ a b c ENSG00000238114, ENSG00000236925, ENSG00000231314, ENSG00000204487, ENSG00000236237, ENSG00000227507, ENSG00000206437 GRCh38: Ensembl release 89: ENSG00000223448, ENSG00000238114, ENSG00000236925, ENSG00000231314, ENSG00000204487, ENSG00000236237, ENSG00000227507, ENSG00000206437 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024399 – 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.
- ^ Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, et al. (Mar 1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell. 72 (6): 847–856. doi:10.1016/0092-8674(93)90574-A. PMID 7916655. S2CID 28961163.
- ^ Browning JL, Androlewicz MJ, Ware CF (Aug 1991). "Lymphotoxin and an associated 33-kDa glycoprotein are expressed on the surface of an activated human T cell hybridoma". Journal of Immunology. 147 (4). Baltimore, Md.: 1230–1237. doi:10.4049/jimmunol.147.4.1230. PMID 1714477. S2CID 6160376.
- ^ a b c "Entrez Gene: LTB lymphotoxin beta (TNF superfamily, member 3)".
- ^ Korneev K, Atretkhany K, Drutskaya M, Grivennikov S, Kuprash D, Nedospasov S (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis". Cytokine. 89: 127–135. doi:10.1016/j.cyto.2016.01.021. PMID 26854213.
- ^ Williams-Abbott L, Walter BN, Cheung TC, Goh CR, Porter AG, Ware CF (Aug 1997). "The lymphotoxin-alpha (LTalpha) subunit is essential for the assembly, but not for the receptor specificity, of the membrane-anchored LTalpha1beta2 heterotrimeric ligand". The Journal of Biological Chemistry. 272 (31): 19451–19456. doi:10.1074/jbc.272.31.19451. PMID 9235946.
- ^ Browning JL, Sizing ID, Lawton P, Bourdon PR, Rennert PD, Majeau GR, et al. (Oct 1997). "Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes". Journal of Immunology. 159 (7). Baltimore, Md.: 3288–3298. doi:10.4049/jimmunol.159.7.3288. PMID 9317127. S2CID 25608697.
- ^ Browning JL, Dougas I, Ngam-ek A, Bourdon PR, Ehrenfels BN, Miatkowski K, et al. (Jan 1995). "Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors". Journal of Immunology. 154 (1). Baltimore, Md.: 33–46. doi:10.4049/jimmunol.154.1.33. PMID 7995952. S2CID 22313274.
Further reading
- Messer G, Spengler U, Jung MC, Honold G, Blömer K, Pape GR, et al. (Jan 1991). "Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production". The Journal of Experimental Medicine. 173 (1): 209–219. doi:10.1084/jem.173.1.209. PMC 2118757. PMID 1670638.
- Abraham LJ, Du DC, Zahedi K, Dawkins RL, Whitehead AS (1991). "Haplotypic polymorphisms of the TNFB gene". Immunogenetics. 33 (1): 50–53. doi:10.1007/BF00211695. PMID 1671667. S2CID 38756894.
- Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, et al. (Sep 1985). "Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization". Nucleic Acids Research. 13 (17): 6361–6373. doi:10.1093/nar/13.17.6361. PMC 321958. PMID 2995927.
- Holzinger I, de Baey A, Messer G, Kick G, Zwierzina H, Weiss EH (1995). "Cloning and genomic characterization of LST1: a new gene in the human TNF region". Immunogenetics. 42 (5): 315–322. doi:10.1007/BF00179392. PMID 7590964. S2CID 19916860.
- Peelman LJ, Chardon P, Nunes M, Renard C, Geffrotin C, Vaiman M, et al. (Mar 1995). "The BAT1 gene in the MHC encodes an evolutionarily conserved putative nuclear RNA helicase of the DEAD family". Genomics. 26 (2): 210–218. doi:10.1016/0888-7543(95)80203-X. PMID 7601445.
- Browning JL, Dougas I, Ngam-ek A, Bourdon PR, Ehrenfels BN, Miatkowski K, et al. (Jan 1995). "Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors". Journal of Immunology. 154 (1). Baltimore, Md.: 33–46. doi:10.4049/jimmunol.154.1.33. PMID 7995952. S2CID 22313274.
- Albertella MR, Campbell RD (May 1994). "Characterization of a novel gene in the human major histocompatibility complex that encodes a potential new member of the I kappa B family of proteins". Human Molecular Genetics. 3 (5): 793–799. doi:10.1093/hmg/3.5.793. PMID 8081366.
- Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, et al. (Feb 1993). "Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment". Nature Genetics. 3 (2): 137–145. doi:10.1038/ng0293-137. PMID 8499947. S2CID 33041319.
- Nakamura T, Tashiro K, Nazarea M, Nakano T, Sasayama S, Honjo T (Nov 1995). "The murine lymphotoxin-beta receptor cDNA: isolation by the signal sequence trap and chromosomal mapping". Genomics. 30 (2): 312–319. doi:10.1006/geno.1995.9872. hdl:2433/202166. PMID 8586432.
- Utans U, Quist WC, McManus BM, Wilson JE, Arceci RJ, Wallace AF, et al. (May 1996). "Allograft inflammatory factory-1. A cytokine-responsive macrophage molecule expressed in transplanted human hearts". Transplantation. 61 (9): 1387–1392. doi:10.1097/00007890-199605150-00018. PMID 8629302.
- Nalabolu SR, Shukla H, Nallur G, Parimoo S, Weissman SM (Jan 1996). "Genes in a 220-kb region spanning the TNF cluster in human MHC". Genomics. 31 (2): 215–222. doi:10.1006/geno.1996.0034. PMID 8824804.
- Laham N, Van Dunné F, Abraham LJ, Farrugia W, Bendtzen K, Brennecke SP, et al. (Apr 1997). "Tumor necrosis factor-beta in human pregnancy and labor". Journal of Reproductive Immunology. 33 (1): 53–69. doi:10.1016/S0165-0378(97)01012-7. PMID 9185077.
- Warzocha K, Renard N, Charlot C, Bienvenu J, Coiffier B, Salles G (Sep 1997). "Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas". Biochemical and Biophysical Research Communications. 238 (2): 273–276. doi:10.1006/bbrc.1997.7277. PMID 9299492.
- Browning JL, Sizing ID, Lawton P, Bourdon PR, Rennert PD, Majeau GR, et al. (Oct 1997). "Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes". Journal of Immunology. 159 (7). Baltimore, Md.: 3288–3298. doi:10.4049/jimmunol.159.7.3288. PMID 9317127. S2CID 25608697.
- de Baey A, Fellerhoff B, Maier S, Martinozzi S, Weidle U, Weiss EH (Nov 1997). "Complex expression pattern of the TNF region gene LST1 through differential regulation, initiation, and alternative splicing". Genomics. 45 (3): 591–600. doi:10.1006/geno.1997.4963. PMID 9367684.
- Shiina T, Tamiya G, Oka A, Yamagata T, Yamagata N, Kikkawa E, et al. (Feb 1998). "Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region". Genomics. 47 (3): 372–382. doi:10.1006/geno.1997.5114. PMID 9480751.
- Bodor J, Habener JF (Apr 1998). "Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes". The Journal of Biological Chemistry. 273 (16): 9544–9551. doi:10.1074/jbc.273.16.9544. PMID 9545284.
- Neville MJ, Campbell RD (Apr 1999). "A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC". Journal of Immunology. 162 (8). Baltimore, Md.: 4745–4754. doi:10.4049/jimmunol.162.8.4745. PMID 10202016. S2CID 46517924.
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| By family | |
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By function/
cell | |
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| LTB (TNFβ) |
- Decoy receptors: Baminercept
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| TNF (TNFα) | | TNFR1 |
- Agonists: Plusonermin
- Sonermin
- Tasonfermin
- TNF (TNFα)
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| TNFR2 |
- Agonists: Plusonermin
- Sonermin
- Tasonfermin
- TNF (TNFα)
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| Ungrouped |
- Enzyme inhibitors: Apratastat
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| Others |
- TNF superfamily protein ligands: 4-1BBL (CD137L, TNFSF9)
- APRIL (CD256, TNFSF13)
- BAFF (CD257, TNFSF13B)
- CAML
- CD70 (CD27L, TNFSF7)
- CD153 (CD30L, TNFSF8)
- CD154 (CD40L, TNFSF5)
- Ectodysplasin (A, A2)
- FasL (CD95L, TNFSF6)
- GITRL (TNFSF18)
- LIGHT (HEVML, CD258, TNFSF14)
- OX40L (CD252, TNFSF4)
- RANKL (TRANCE, OPGL, ODF, CD254, TNFSF11)
- Siva (CD27BP)
- TRAIL (CD253, TNFSF10)
- TWEAK (TNFSF12)
- VEGI (TL1A, TNFSF15)
- Recombinant proteins: Ardenermin
- Dulanermin
- Decoy receptors: Briobacept
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