Transglutaminase Cross-Links Sp1-Mediated Transcription to Ethanol-Induced Liver Injury  Pavel Strnad, M. Bishr Omary  Gastroenterology  Volume 136, Issue 5, Pages 1502-1505 (May 2009) DOI: 10.1053/j.gastro.2009.03.021 Copyright © 2009 AGA Institute Terms and Conditions

Figure 1 TG2, a multifaceted enzyme, plays an important role in liver injury. (A) TG2 is involved in 3 major enzymatic conversions: (i) posttranslational modification of specific glutamines of protein substrates by covalent linkage to other proteins (or potentially to themselves) via a reaction termed transamidation, (ii) deamidation of glutamines on proteins to form glutamic acid, and (iii) covalent linkage to soluble amines such as polyamines.7,9 (B) Stress situations, such as ethanol exposure or Fas ligand, result in enhanced cross-linking activity and transamidation of multiple proteins. One affected pathway is the Sp1–c-met axis, which was demonstrated in the study by Tatsukawa et al.6 Another TG2 hepatocyte substrate is keratin 8 whose cross-linking results in the formation of Mallory-Denk bodies (MDBs) that are found in human alcoholic and nonalcoholic steatohepatitis.18 Gastroenterology 2009 136, 1502-1505DOI: (10.1053/j.gastro.2009.03.021) Copyright © 2009 AGA Institute Terms and Conditions