Latency, activation, and binding proteins of TGF-beta
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Updated: Oct 9, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
K Koli1, J Saharinen, M Hyytiäinen
1Department of Virology, Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland. Katri.koli@helsinki.Fi
Abstract:
The TGF-beta superfamily of growth factors consists of an increasing number of different polypeptide modulators of cell growth, differentiation, and morphogenesis. Three mammalian isoforms have been molecularly cloned. Numerous ways to regulate the expression of the TGF-beta genes have been identified. TGF-betas are, for example, subject to regulation by retinoids, steroid hormones, and vitamin D. A characteristic feature in the biology of TGF-betas is that they are usually secreted from cells in latent forms. The large latent complex consists of the small latent complex (TGF-beta and its propeptide) and a high molecular weight protease resistant binding protein, latent TGF-beta binding protein (LTBP). LTBPs are required for the proper folding and secretion of TGF-beta. TGF-beta is not just secreted from cultured cells but is deposited via LTBPs to the pericellular space, namely to the extracellular matrix. Release of these complexes and activation by proteases is under tight regulation and provides a means to rapidly increase local concentrations of TGF-beta. Biological events, where enhanced or focal proteolysis and activation of latent TGF-beta takes place, include cell invasion, tissue remodeling, and wound healing.
Insights
Transforming Growth Factor-beta (TGF-beta) superfamily proteins are key regulators of cell functions. They are secreted in latent complexes, requiring proteases for activation in processes like tissue remodeling.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The Transforming Growth Factor-beta (TGF-beta) superfamily comprises diverse polypeptide modulators crucial for cell growth, differentiation, and morphogenesis.
- Three mammalian TGF-beta isoforms have been identified and molecularly cloned.
- TGF-beta gene expression is regulated by various factors, including retinoids, steroid hormones, and vitamin D.
Purpose of the Study:
- To elucidate the secretion and activation mechanisms of TGF-beta.
- To understand the role of latent TGF-beta binding proteins (LTBPs) in TGF-beta biology.
- To explore the significance of TGF-beta activation in physiological processes.
Main Methods:
- Molecular cloning of TGF-beta isoforms.
- Analysis of TGF-beta gene regulation.
- Investigation of TGF-beta secretion pathways.
- Characterization of latent TGF-beta complexes and LTBP interactions.
Main Results:
- TGF-betas are secreted in latent forms, typically as large latent complexes involving LTBP.
- LTBPs are essential for correct TGF-beta folding and secretion.
- TGF-beta is deposited into the extracellular matrix via LTBPs.
- Proteolytic release and activation of latent TGF-beta are tightly regulated.
Conclusions:
- TGF-beta activation, regulated by proteolysis, allows for rapid increases in local TGF-beta concentrations.
- This activation mechanism is critical in biological events such as cell invasion, tissue remodeling, and wound healing.
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