Tissue transglutaminase, a key enzyme involved in liver diseases.

Ubiquitous tissue transglutaminase (tTG) is one member of the large transglutaminase (TG) family, which catalyze posttranslational modification of proteins by establishing epsilon(gamma-glutamyl)lysine cross-linking and/or covalent incorporation of polyamines. The unique characteristics of tTG include: (1) possessing both cross-linking activity and GTPase activity; (2) functioning as a G protein; and (3) participating in the signal transduction of alpha1-adrenergic receptor coupling. A growing body of literature suggests that increased tTG levels in the cytosolic or nuclear compartments contribute to the apoptotic process, and lines of evidence exist that nuclear translocation and cross-linking of transcriptional factor Sp1 may represent the underlying mechanisms of these proapoptotic effects of tTG. Our studies indicate that tTG GTPase activation may be responsible for enhanced hepatocyte proliferation, whereas, its tTGase activity may cause increased apoptosis. Moreover, it appears that tTG cross-linking activity contributes to hepatic fibrogenesis in animal models and in human liver disease. Understanding the roles of tTG in the pathogenesis of liver disease could facilitate the development of new treatment regimens.