Transglutaminase 2 (TGase2) is a ubiquitously expressed enzyme that catalyzes irreversible post-translational modification of protein, forming cross-linked protein aggregates. We previously reported that intracellular TGase2 is activated by oxidative stress. To elucidate the functional role of TGase2 activation in cells under the oxidatively stressed condition, we identified the mediator that activates TGase2. In this study, we showed that low levels of oxidative stress trigger the release of TGF beta, which subsequently activates TGase2 through the nuclear translocation of Smad3. Analysis of substrate proteins reveals that TGase2-mediated protein modification results in a decrease of protein solubility and a collapse of intermediate filament network, which leads to aggregation of proteins. We confirm these results using lens tissues from TGase2-deficient mice. Among several antioxidants tried, only N-acetylcysteine effectively inhibits TGF beta-mediated activation of TGase2. These results indicate that TGF beta mediates oxidative stress-induced protein aggregation through activation of TGase2 and suggest that the formation of protein aggregation may not be a passive process of self-assembly of oxidatively damaged proteins but may be an active cellular response to oxidative stress. Therefore, TGF beta-TGase2 pathway may have implications for both the pathogenesis of age-related degenerative diseases and the development of pharmaceutics.
Shin DM, J.J. (2008). TGF beta mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation. THE FASEB JOURNAL, 22(7), 2498-2507.
|Tipologia:||Articolo su rivista|
|Citazione:||Shin DM, J.J. (2008). TGF beta mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation. THE FASEB JOURNAL, 22(7), 2498-2507.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/11|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1096/fj.07-095455|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2008|
|Titolo:||TGF beta mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation|
|Autori:||Shin DM, Jeon JH, Kim CW, Cho SY, Lee HJ, Jang GY, Jeong EM, Lee DS, Kang JH, Melino G, Park SC, Kim IG.|
|Appare nelle tipologie:||01 - Articolo su rivista|