Biology:Transforming growth factor, beta 3

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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

Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene.[1][2]

It is a type of protein, known as a cytokine, which is involved in cell differentiation, embryogenesis and development. It belongs to a large family of cytokines called the Transforming growth factor beta superfamily, which includes the TGF-β family, Bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), inhibins and activins.[3]

TGF-β3 is believed to regulate molecules involved in cellular adhesion and extracellular matrix (ECM) formation during the process of palate development. Without TGF-β3, mammals develop a deformity known as a cleft palate.[4][5] This is caused by failure of epithelial cells in both sides of the developing palate to fuse. TGF-β3 also plays an essential role in controlling the development of lungs in mammals, by also regulating cell adhesion and ECM formation in this tissue,[6] and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin.[1]

Interactions

Transforming growth factor, beta 3 has been shown to interact with TGF beta receptor 2.[7][8][9][10]

Clinical research

After successful phase I/II trials,[11] human recombinant TGF-β3 (Avotermin, planned trade name Juvista) failed in Phase III trials.[12]

References

  1. ↑ 1.0 1.1 "A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing". The Journal of Cell Biology 172 (7): 1093–105. Mar 2006. doi:10.1083/jcb.200507111. PMID 16549496. 
  2. ↑ "Entrez Gene: TGFB3 transforming growth factor, beta 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7043. 
  3. ↑ "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Developmental and Comparative Immunology 28 (5): 461–85. May 2004. doi:10.1016/j.dci.2003.09.007. PMID 15062644. 
  4. ↑ "Pathogenesis of cleft palate in TGF-beta3 knockout mice". Development 126 (17): 3869–79. Sep 1999. doi:10.1242/dev.126.17.3869. PMID 10433915. 
  5. ↑ "Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway". Developmental Biology 266 (1): 96–108. Feb 2004. doi:10.1016/j.ydbio.2003.10.007. PMID 14729481. 
  6. ↑ "Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction". Nature Genetics 11 (4): 415–21. Dec 1995. doi:10.1038/ng1295-415. PMID 7493022. 
  7. ↑ "Transforming growth factor-beta (TGF-beta) binding to the extracellular domain of the type II TGF-beta receptor: receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding". Journal of Molecular Biology 328 (5): 1173–83. May 2003. doi:10.1016/S0022-2836(03)00360-7. PMID 12729750. 
  8. ↑ "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology 9 (3): 203–8. Mar 2002. doi:10.1038/nsb766. PMID 11850637. 
  9. ↑ "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry 274 (2): 584–94. Jan 1999. doi:10.1074/jbc.274.2.584. PMID 9872992. 
  10. ↑ "Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor". The EMBO Journal 20 (3): 480–90. Feb 2001. doi:10.1093/emboj/20.3.480. PMID 11157754. 
  11. ↑ "Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies". Lancet 373 (9671): 1264–74. Apr 2009. doi:10.1016/S0140-6736(09)60322-6. PMID 19362676. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60322-6/abstract. 
  12. ↑ Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints, 14 February 2011

Further reading

External links



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