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Fibrillin controls TGF-β activation

Nature Genetics volume 33, pages 331–332 (2003)Cite this article

Secreted transforming growth factor-βs (TGF-βs) are rendered biologically inactive by binding proteins that also target and concentrate them to the extracellular matrix. Specific, but still poorly understood, activation is required for disassembly of the extracellular matrix–bound protein complex to liberate the mature growth factor and to obtain a correct biological effect. A new study shows that fibrillin-1, the protein defective in Marfan syndrome, has a biologically important role in controlling TGF-β activation in the lung.

TGF-βs (refs. 1–3) are multifunctional growth factors that are capable of inducing a spectrum of cellular events including proliferation, cell cycle arrest, differentiation, programmed cell death and matrix deposition1. They are synthesized as prepropolypeptides that are proteolytically processed in the Golgi apparatus to a mature growth factor and its propeptide, also known as the latency associated peptide (LAP). Dimers of mature TGF-β and LAP form a tight complex, termed the small latent complex (SLC), that is biologically inactive. The SLC is covalently bound to another protein called latent TGF-β binding protein (LTBP), forming the large latent complex (LLC). The LLC is secreted from cells to the extracellular space, where it binds to the extracellular matrix (see figure; refs. 2,3).

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  1. Developmental Biology Program, Children's Hospital Los Angeles Research Institute, USC Keck School of Medicine and School of Dentistry, Los Angeles, 90027, California, USA

    Vesa Kaartinen & David Warburton

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  1. Vesa Kaartinen
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  2. David Warburton
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Correspondence to David Warburton.

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Kaartinen, V., Warburton, D. Fibrillin controls TGF-β activation. Nat Genet 33, 331–332 (2003). https://doi.org/10.1038/ng0303-331

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