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Synonyms: TGF-beta-1 | transforming growth factor beta-1
Compound class: Endogenous peptide in human, mouse or rat
Comment: TGFβ is a labile (half-life in vivo of 2-3 minutes) but highly potent cytokine. It plays a crucial role in immune regulation, and is highly fibriogenic.
The TGFβ1 gene encodes a proprotein that contains sequences for the latency-associated peptide (LAP) and the TGFβ peptide chains. Amino acids 1-29 form the signal peptide, 30-278 represent LAP and the C-terminal amino acids from 279-390 form TGFβ.
TGFβ is expressed at the cell surface (e.g. on Treg cells) as a highly glycosylated, furin-processed product in complex with the LAP protein. This complex does not have biological activity (so is a.k.a. latent TGFβ) and requires further processing to produce active TGFβ [4,6].
1. Chen ML, Yan BS, Bando Y, Kuchroo VK, Weiner HL. (2008)
Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis.
J. Immunol., 180 (11): 7327-37. [PMID:18490732]
2. Gabriely G, da Cunha AP, Rezende RM, Kenyon B, Madi A, Vandeventer T, Skillin N, Rubino S, Garo L, Mazzola MA et al.. (2017)
Targeting latency-associated peptide promotes antitumor immunity.
Sci Immunol, 2 (11). [PMID:28763794]
3. Ledbetter SR, Hart CP, Holgate RG, Jermutus LU, Buchanan CL, Duncan AR, Finch DK. (2010)
Antibodies to TGF-[beta].
Patent number: US7723486. Assignee: Optein, Inc., Genzyme Corporation. Priority date: 08/02/2005. Publication date: 25/05/2010.
4. Nakamura K, Kitani A, Strober W. (2001)
Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta.
J. Exp. Med., 194 (5): 629-44. [PMID:11535631]
5. Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, Wu H, Chen ML, Gandhi R, Miller A et al.. (2006)
Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells.
Nat. Med., 12 (6): 627-35. [PMID:16715091]
6. Oida T, Weiner HL. (2010)
Overexpression of TGF-ß 1 gene induces cell surface localized glucose-regulated protein 78-associated latency-associated peptide/TGF-ß.
J. Immunol., 185 (6): 3529-35. [PMID:20720212]
7. Weiner HL, Gabriely G, Da Cunha AP. (2016)
Treatment of cancer with anti-lap monoclonal antibodies.
Patent number: WO2016115345A1. Assignee: The Brigham And Women's Hospital. Priority date: 14/01/2015. Publication date: 21/07/2016.