Biology:Lymphotoxin beta

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


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


Lymphotoxin-beta (LT-beta) also known as tumor necrosis factor C (TNF-C) is a protein that in humans is encoded by the LTB gene.[1][2][3]

Function

Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lymphotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms.[3]

Pro-tumorigenic function of membrane LT is clearly established: mice with overexpression of LTα or LTβ showed increased tumor growth and metastasis in several models of cancer. However, these studies utilized mice with complete LTα gene deficiency that did not allow to distinguish effects of soluble versus membrane-associated LT.[4]

Interactions

LTB has been shown to interact with Lymphotoxin alpha.[5][6][7]

References

  1. "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell 72 (6): 847–56. Mar 1993. doi:10.1016/0092-8674(93)90574-A. PMID 7916655. 
  2. "Lymphotoxin and an associated 33-kDa glycoprotein are expressed on the surface of an activated human T cell hybridoma". Journal of Immunology 147 (4): 1230–7. Aug 1991. doi:10.4049/jimmunol.147.4.1230. PMID 1714477. 
  3. 3.0 3.1 "Entrez Gene: LTB lymphotoxin beta (TNF superfamily, member 3)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4050. 
  4. Korneev, KV; Atretkhany, KN; Drutskaya, MS; Grivennikov, SI; Kuprash, DV; Nedospasov, SA (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. 
  5. "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): 19451–6. Aug 1997. doi:10.1074/jbc.272.31.19451. PMID 9235946. 
  6. "Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes". Journal of Immunology 159 (7): 3288–98. Oct 1997. doi:10.4049/jimmunol.159.7.3288. PMID 9317127. 
  7. "Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors". Journal of Immunology 154 (1): 33–46. Jan 1995. doi:10.4049/jimmunol.154.1.33. PMID 7995952. 

Further reading