Figure 2.

Regulation of TG2 expression and activity. (A) Several factors bind to the TGM2 promoter and regulate TGM2 expression. Response elements binding sites for retinoic acid, RXR/RAR (−1731 bp and −1720 bp), glucocorticoids, GRE (−1399 bp), NF-κB (−1338 bp), IL-6 (−1190 bp), TGF-β1 (−900 bp), estrogens, ERE (−656 bp), activator protein-2, AP-2 (−634 bp), hypoxia: HRE (−367 bp), activator protein-1, AP-1, and nuclear factor-1 (+4 bp, +12 bp) as well as motif regions such as CAAT box (−96 bp), TATA box (−29 bp), GC box, (Sp1, −54 bp, −43 bp, +59 bp, +65 bp) are indicated. (B) The balance between open and closed TG2 structural conformations is mainly regulated by Ca²⁺ and GTP concentrations. In the open conformation, TG2 transamidase activity is enhanced by thioredoxin, SUMOylation, and membrane lipids (sphingosylphosphocholine), whereas it is inhibited by S-nitrosylation and acetylation.