Tissue transglutaminase and the stress response

Abstract

The expression of the protein crosslinking enzyme tissue transglutaminase (TG2, tTG), the ubiquitous member of transglutaminase family, can be regulated by multiple factors. Although it has been suggested that TG2 can be involved in apoptotic cell death, high levels of enzyme have also been associated with cell survival in response to different stimuli. Furthermore, evidence indicates that increases in TG2 production cause enzyme translocation to cell membrane. Cell stress can also lead to TG2 accumulation on the cell surface and in the extracellular matrix resulting in changes in cell-matrix interactions.Here, we discuss the underlying mechanisms of TG2 up-regulation induced by various stimuli including glutamate exposure, calcium influx, oxidative stress, UV, and inflammatory cytokines. These findings agree with a postulated role for transglutaminases in molecular mechanisms involved in several diseases suggesting that cross-linking reactions could be a relevant part of the biochemical changes observed in pathological conditions.

Posttranslational Modification of HLA-DQ Binding Islet Autoantigens in Type 1 Diabetes

“…Gene and protein expression of tTG has been found in human pancreatic cancer cell lines (35,36). Electron microscopy has shown that tTG is localized close to insulin and glucagon granules in human pancreatic islets (37,38), is expressed in antigen-presenting cells (39), that this tTG is active (40), and that various stimuli or insults that induce cell stress (e.g., inflammation) are able to activate tTG (41). Although deamidated proinsulin has not been detected in human islets by MS (42,43), it is conceivable that calcium levels change during ER stress in b-cells and T-cell death, creating the conditions required for tTG activation and resulting in the modification of islet autoantigens.…”

The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

“…The take home message has been that TG2 expression and activity is generally altered when the tumour cells are compared to normal cells (Ientile et al 2007;Kotsakis and Griffin 2007). Whether this is an increase or a reduction in TG2 activity either through reduced expression or the expression of altered forms (Di Giacomo et al 2009) seems to be dependent on tumour type and stage of tumour progression.…”

Amyloid β in hereditary cerebral hemorrhage with amyloidosis-Dutch type

“…tTG is an enzyme involved in posttranslational modifications of proteins, like covalently cross-linked proteins (Lorand and Graham, 2003). It plays an important role in the remodeling of the ECM after tissue injury and cell stress (Ientile et al, 2007). It is known that tTG mediates Aβ40 dimerization through covalent intermolecular cross-linking and thereby seeding aggregation (Schmid et al, 2011).…”