Structure and Regulation of Type 2 Transglutaminase in Relation to its Physiological Functions and Pathological Roles

Effects of the regulatory ligands calcium and GTP on the thermal stability of tissue transglutaminase

“…Most recent evidences, that support a major role of tissue transglutaminase in the pathogenesis of autoimmune and neurodegenerative diseases (Iismaa et al 2009), have greatly stimulated interest in this multifunctional enzyme, subjected to complex regulation by transcriptional and by allosteric mechanisms (Griffin et al 2002;Bergamini et al 2011). The pathologic relevance of transglutaminase is largely related to an increase in transamidation activity, which can arise through deregulated activity of a normal amount of cellular enzyme (Monsonego et al 1998) or through an increased number of enzyme molecules inside the cells.…”

“…Actually the physiologic function of tissue transglutaminase is a still unresolved issue and is also influenced by the enzyme cellular location (Gundemir and Johnson 2009;Bergamini et al 2011). In relation to function within the intracellular space, it has been proposed that the enzyme is mainly involved in controlling the programs of cell death and proliferation (Fesus and Szondy 2005;Bergamini et al 2010).…”

“…Several studies indicate that tissue transglutaminase is a bifunctional enzyme displaying activities of GTP hydrolysis and of protein transamidation in an alternative switching-on pattern (Griffin et al 2002). Interestingly, transamidation is usually inactive because it requires nearmillimolar concentrations of calcium ions and breakdown of cell GTP, which is an inhibitor, conditions that are usually not met in the intracellular compartment (Bergamini et al 2011).…”

Expression of Functional Recombinant Human Tissue Transglutaminase (TG2) Using the Bac-to-Bac Baculovirus Expression System

“…TG2 might be an attractive novel pharmacological target for treatment of neurodegenerative diseases in preventing toxic protein aggregation. 13 Although many studies about the diverse aspects of tissue transglutaminase (TG2) specially its roles in pathobiology of diseases have been reported, 2,7,14 there have not been much reports on the enzyme inhibitors. For this reason the expression of recombinant human TG2 enzyme as well as the assessment of its in vitro biological activity has been undertaken in the present study.…”

Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives

“…One attractive possibility is that these pleomorphic actions of TGases are linked to selective triggering of alternative activities (Bergamini et al 2011;Gundemir et al 2012) such as transamidation, G-protein signaling, scaffolding, or interaction with other proteins because of alternative splicing or location to different environments including intra-or extracellular space, to which it can gain access through still undefined pathways. Three communications focus these aspects.…”