Type 2 Transglutaminase and Cell Death

Piacentini, Mauro; Amendola, Alessandra; Ciccosanti, Fabiola; Falasca, Laura; Farrace, Maria Grazia; Mastroberardino, Pier G.; Nardacci, Roberta; Oliverio, Serafina; Piredda, Lucia; Rodolfo, Carlo; Autuori, Francesco

doi:10.1159/000084233

Cited by 35 publications

(26 citation statements)

References 73 publications

(143 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to these findings, 4-HR had synergistic effects along with cisplatin on KB cell death. tg-2 localizes mainly in the cytoplasm, yet recent reports also suggest its presence in the nucleus, mitochondria, at the cell surface, and in the extracellular matrix (20). nuclear localization of tg-2 is associated with high levels of increased tg activity (21).…”

Section: Discussionmentioning

confidence: 96%

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

Kim

Jeong²,

Park³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. resistance to chemotherapy is very important in the prognosis of tumors. transglutaminase-2 (tg-2) mediated chemotherapy resistance has been widely reported. the objective of this study was to demonstrate the effect of 4-hexylresorcinol (4-Hr) on tg-2 activity in nasopharyngeal squamous cell carcinoma cells (KB cells). treatment with a mixture of 4-HR and cisplatin significantly decreased KB cell viability compared to treatment by cisplatin alone at 10 µg/ml (p<0.001). 4-Hr inhibited tg-2 activity compared to cisplatin alone at 5, 10 and 20 µg/ml (p=0.001, 0.001 and 0.003, respectively). nuclear translocation of tg-2 was also inhibited by 4-Hr treatment. 4-Hr treatment also increased the fluorescence life-time of DAPI significantly compared to the untreated control or the cisplatin treated group (p<0.001).In conclusion, 4-HR inhibited TG-2 activity and showed a synergistic effect on tumor cell growth inhibition with cisplatin.

show abstract

Section: Discussionmentioning

confidence: 96%

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

Kim

Jeong²,

Park³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…1,2 In addition, it may also act as a G protein in transmembrane signaling, as a kinase, as a protein disulphide isomerase and as a cell surface adhesion mediator. 1,2 The vast array of biochemical functions catalyzed by TG2 distinguishes it from the other members of the transglutaminase family. Multiple lines of evidence suggest an involvement of the enzyme in neurodegenerative diseases, such as Huntington (HD) and Parkinson (PD), heart failure, infectious diseases and cancer.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] Interestingly, autophagy has been shown to play an essential role, whether the pathogenesis of all these deseases or in the response to them, thus suggesting a possible participation of TG2 in this "self-digestion" pathway. 2,[6][7][8] In particular, recent reports have demonstrated that multiple forms of cardiovascular stress, including pressure overload, chronic ischemia and infarction-reperfusion injury, provoke an increase in autophagic activity in cardiomyocytes. 9, 10 We have shown that ablation of TG2 in mice causes an increased vulnerability of cardiomyocytes to ischemia/reperfusion injury.…”

Section: Introductionmentioning

confidence: 99%

Transglutaminase 2 is involved in autophagosome maturation

D’Eletto¹,

Farrace²,

Falasca³

et al. 2009

Autophagy

Self Cite

View full text Add to dashboard Cite

“…As a consequence, the enzyme is likely to be inactive under normal Ca 2ϩ homeostasis. TG2 localizes mainly in the cytoplasm, yet recent reports also suggest its presence in the nucleus, mitochondria, at the cell surface, and in the extracellular matrix (ECM) (1)(2)(3). TG2 is translocated to the plasma membrane and was subsequently deposited into the ECM via a non-classical secretory mechanism reportedly dependent on active site conformation and on an intact N-terminal ␤-sandwich domain (4, 5) as well as on its possible association with integrins (6).…”

mentioning

confidence: 99%

Fibronectin-Tissue Transglutaminase Matrix Rescues RGD-impaired Cell Adhesion through Syndecan-4 and β1 Integrin Co-signaling

Telci

Wang

et al. 2008

Journal of Biological Chemistry

120

169

View full text Add to dashboard Cite

Heterotropic association of tissue transglutaminase (TG2) with extracellular matrix-associated fibronectin (FN) can restore the adhesion of fibroblasts when the integrin-mediated direct binding to FN is impaired using RGD-containing peptide. We demonstrate that the compensatory effect of the TG-FN complex in the presence of RGD-containing peptides is mediated by TG2 binding to the heparan sulfate chains of the syndecan-4 cell surface receptor. This binding mediates activation of protein kinase C␣ (PKC␣) and its subsequent interaction with ␤ 1 integrin since disruption of PKC␣ binding to ␤ 1 integrins with a cell-permeant competitive peptide inhibits cell adhesion and the associated actin stress fiber formation. Cell signaling by this process leads to the activation of focal adhesion kinase and ERK1/2 mitogen-activated protein kinases. Fibroblasts deficient in Raf-1 do not respond fully to the TG-FN complex unless either the full-length kinase competent Raf-1 or the kinase-inactive domain of Raf-1 is reintroduced, indicating the involvement of the Raf-1 protein in the signaling mechanism. We propose a model for a novel RGD-independent cell adhesion process that could be important during tissue injury and/or remodeling whereby TG-FN binding to syndecan-4 activates PKC␣ leading to its association with ␤ 1 integrin, reinforcement of actin-stress fiber organization, and MAPK pathway activation. Tissue transglutaminase (TG2)2 belongs to a family of enzymes that in the presence of Ca 2ϩ catalyze the post-translational modification of proteins either by covalent cross-linking or through the incorporation of primary amines. TG2 has a GTP binding/hydrolysis site that negatively modulates the Ca 2ϩ -dependent transamidating activity of the enzyme by obstructing access to the active site (1). As a consequence, the enzyme is likely to be inactive under normal Ca 2ϩ homeostasis. TG2 localizes mainly in the cytoplasm, yet recent reports also suggest its presence in the nucleus, mitochondria, at the cell surface, and in the extracellular matrix (ECM) (1-3). TG2 is translocated to the plasma membrane and was subsequently deposited into the ECM via a non-classical secretory mechanism reportedly dependent on active site conformation and on an intact N-terminal ␤-sandwich domain (4, 5) as well as on its possible association with integrins (6). Deposition of the enzyme into the ECM after cell damage and stress is important in the remodeling and/or stabilization of the several ECM proteins, such as FN (7,8). FN is particularly interesting since TG2 binds to this ECM protein with high affinity promoting wideranging effects on cell-matrix interactions, including the regulation of cell adhesion and migration, matrix assembly, and adhesion-dependent signaling (6,7,9).Cell adhesion to FN involves a series of coordinated signaling events orchestrated by numerous transmembrane receptors including the integrins and the superfamily of cell-surface proteoglycans (10, 11). The identity of the receptor-ligand pairing defines the composition of f...

show abstract

Type 2 Transglutaminase and Cell Death

Cited by 35 publications

References 73 publications

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells

Transglutaminase 2 is involved in autophagosome maturation

Fibronectin-Tissue Transglutaminase Matrix Rescues RGD-impaired Cell Adhesion through Syndecan-4 and β1 Integrin Co-signaling

Contact Info

Product

Resources

About