Regulation of Transglutaminase 2 by Oxidative Stress

摘要: Transglutaminase 2 (TG2) is an enzyme that transamidates glutamine residue in its substrates, resulting the accumulation of crosslinked, monoaminated, polyaminated, or deamidated protein products. Recent evidence has suggested aberrant regulation TG2 by oxidative stress causes various disorders including cataract formation, inflammation, fibrosis, celiac disease, neurodegenerative diseases, and diabetes mellitus. In this chapter, we describe how responds to participates disease pathogeneses following three ways. First, expression level increased stress-mediated activation transcription factors, NF-κB hypoxia-inducible factor 1. Second, induces post-translational modifications (PTMs) forming intramolecular disulfides, SUMOylation, ubiquitination, while nitrosative promotes S-nitrosylation. This regulates transamidation activity, stability, subcellular localization TG2. Finally, stress-responsive cellular mediators like intracellular calcium ions, transforming growth β, newly identified endogenous inhibitor proteins can modulate enzymatic activity. Elucidating regulatory mechanisms will increase our understanding precise pathophysiological role related also help establishing therapeutic strategies.