Biology:Lymphotoxin beta

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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.

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.

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.

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.

Interactions

LTB has been shown to interact with Lymphotoxin alpha.

Further reading

• "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. Jan 1991. doi:10.1084/jem.173.1.209. PMID 1670638. 
• "Haplotypic polymorphisms of the TNFB gene". Immunogenetics 33 (1): 50–53. 1991. doi:10.1007/BF00211695. PMID 1671667. 
• "Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization". Nucleic Acids Research 13 (17): 6361–6373. Sep 1985. doi:10.1093/nar/13.17.6361. PMID 2995927. 
• "Cloning and genomic characterization of LST1: a new gene in the human TNF region". Immunogenetics 42 (5): 315–322. 1995. doi:10.1007/BF00179392. PMID 7590964. 
• "The BAT1 gene in the MHC encodes an evolutionarily conserved putative nuclear RNA helicase of the DEAD family". Genomics 26 (2): 210–218. Mar 1995. doi:10.1016/0888-7543(95)80203-X. PMID 7601445. 
• "Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors". Journal of Immunology (Baltimore, Md.) 154 (1): 33–46. Jan 1995. doi:10.4049/jimmunol.154.1.33. PMID 7995952. 
• "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. May 1994. doi:10.1093/hmg/3.5.793. PMID 8081366. 
• "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. Feb 1993. doi:10.1038/ng0293-137. PMID 8499947. 
• "The murine lymphotoxin-beta receptor cDNA: isolation by the signal sequence trap and chromosomal mapping". Genomics 30 (2): 312–319. Nov 1995. doi:10.1006/geno.1995.9872. PMID 8586432. 
• "Allograft inflammatory factory-1. A cytokine-responsive macrophage molecule expressed in transplanted human hearts". Transplantation 61 (9): 1387–1392. May 1996. doi:10.1097/00007890-199605150-00018. PMID 8629302. 
• "Genes in a 220-kb region spanning the TNF cluster in human MHC". Genomics 31 (2): 215–222. Jan 1996. doi:10.1006/geno.1996.0034. PMID 8824804. 
• "Tumor necrosis factor-beta in human pregnancy and labor". Journal of Reproductive Immunology 33 (1): 53–69. Apr 1997. doi:10.1016/S0165-0378(97)01012-7. PMID 9185077. 
• "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. Sep 1997. doi:10.1006/bbrc.1997.7277. PMID 9299492. 
• "Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes". Journal of Immunology (Baltimore, Md.) 159 (7): 3288–3298. Oct 1997. doi:10.4049/jimmunol.159.7.3288. PMID 9317127. 
• "Complex expression pattern of the TNF region gene LST1 through differential regulation, initiation, and alternative splicing". Genomics 45 (3): 591–600. Nov 1997. doi:10.1006/geno.1997.4963. PMID 9367684. 
• "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. Feb 1998. doi:10.1006/geno.1997.5114. PMID 9480751. 
• "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. Apr 1998. doi:10.1074/jbc.273.16.9544. PMID 9545284. 
• "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 (Baltimore, Md.) 162 (8): 4745–4754. Apr 1999. doi:10.4049/jimmunol.162.8.4745. PMID 10202016.