Inactivation of active and latent transforming growth factor beta by free thiols: potential redox regulation of biological action

The International Journal of Biochemistry & Cell Biology
Robert BlakytnyGeorg Brunner

Abstract

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine with important roles in inflammation, wound repair, and cancer. Cells secrete TGF-beta as a latent protein complex, consisting of disulfide-bonded homodimers of growth factor and latency-associated propeptide. Latency regulates extracellular TGF-beta action by controlling the levels of active growth factor available. We report here that active and latent TGF-beta were inactivated in vitro by reduction of the growth factor dimer under physiological conditions. We also demonstrate that the latency-associated propeptide has chaperone-like activity and partially protects TGF-beta from inactivation. TGF-beta inactivation occurred upon incubation with the physiological redox agents, cysteine, homocysteine, and reduced glutathione. Inactivation was temperature- and dose-dependent. While inactivation by physiological concentrations of redox agents was partial at 37 degrees C, active and latent TGF-beta were completely inactivated by raising the temperature in the presence of the redox agents. The mechanism of TGF-beta inactivation involved the generation of biologically inactive growth factor monomer and required the presence of free thiol groups, since thiol bloc...Continue Reading

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Citations

Jan 15, 2010·Biochemistry·Zhonghua Yan, Ruma Banerjee
Sep 1, 2009·Nature Chemical Biology·Zhonghua YanRuma Banerjee
Sep 19, 2009·Nature Chemical Biology·Anna Rubartelli, Roberto Sitia
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Sep 26, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aravind T ReddyRaju C Reddy

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