Disease relevance of Tgm2

• Tissue transglutaminase contributes to disease progression in the R6/2 Huntington's disease mouse model via aggregate-independent mechanisms [1].
• Tetanus toxin potently stimulates tissue transglutaminase. A possible mechanism of neurotoxicity [2].
• Mouse resident peritoneal macrophages, activated in vitro with murine recombinant interferon-gamma and lipopolysaccharide in the presence of sera from different sources, showed marked differences in their abilities to inhibit murine adenocarcinoma cell growth, and in induced activity of the enzyme, tissue transglutaminase [3].
• Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas [4].
• Aryl hydrocarbon receptor (AHR)-null mice display a liver fibrosis phenotype that is associated with a concomitant increase in liver retinoid concentration, tissue transglutaminase type II (TGaseII) activity, transforming growth factor beta (TGF beta) overexpression, and accumulation of collagen [5].

Psychiatry related information on Tgm2

• The protective effects of cystamine in the R6/2 Huntington's disease mouse involve mechanisms other than the inhibition of tissue transglutaminase [6].
• The administration of CD2665 to alcohol-treated mice totally reversed the working memory deficit and suppressed the overexpression of brain RARbeta, RXRbeta/gamma and tTG mRNA, whereas the same treatment in control mice decreased only the RARbeta mRNA level without affecting memory performance [7].

High impact information on Tgm2

• Reticulin, endomysial, and mouse monoclonal tissue transglutaminase antibodies were studied by an indirect immunofluorescence method and gliadin antibodies with ELISA [8].
• Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on cellular morphology and adhesion [9].
• Several cell lines expressing high levels of catalytically active tissue transglutaminase have been isolated and characterized [9].
• Tissue transglutaminase (TGase2) is a protein-crosslinking enzyme known to be associated with the in vivo apoptosis program [10].
• The native cDNA clone and also a mutant form containing a TGC (cysteine) codon in place of TGA were expressed in a baculovirus-insect cell system [11].

Biological context of Tgm2

• Tissue transglutaminase is a multifunctional enzyme that accumulates to high levels in cells undergoing apoptosis [12].
• Using synthetic peptides encompassing this region, we found that the peptide 88WTATVVDQQDCTLSLQLTT106 inhibited the interaction of tissue transglutaminase with fibronectin and decreased transglutaminase-dependent cell adhesion and spreading [13].
• Here we report that in fibroblasts, activated H-Ras and Raf-1 oncogenes decrease biosynthesis, association with beta1 integrins, and surface expression of tTG because of down-regulation of tTG mRNA [14].
• In cell culture models tTG-mediated transamidation positively regulates many processes that occur in vivo during the mammalian brain growth spurt (BGS), including neuronal differentiation, neurite outgrowth, synaptogenesis and cell death mechanisms [15].
• In the current studies, we addressed the temporal course of skeletal muscle tTG gene expression and found maximal expression at birth and continuing into the immediate postnatal period [16].

Anatomical context of Tgm2

• Primary fibroblasts isolated from Tgm2(-/-) mice also showed decreased adherence with culture [17].
• Absence of G(h) coupling to alpha(1)-adrenergic receptor signaling in Tgm2(-/-) mice was demonstrated by the lack of agonist-stimulated [alpha-(32)P]GTP photolabeling of a 74-kDa protein in liver membranes [17].
• In these stably transfected HeLa cells both the endogenous tissue transglutaminase gene and transfected mouse tissue transglutaminase promoter are activated by all-trans retinoic acid and by retinoic acid receptor (RAR)-specific and retinoid X receptor (RXR)-specific retinoids [12].
• Developmental regulation of tissue transglutaminase in the mouse forebrain [15].
• Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis program [18].

Associations of Tgm2 with chemical compounds

• However, with this treatment there was a highly significant decrease in the viability (propidium iodide negativity) of Tgm2(-/-) thymocytes [17].
• Transglutaminase 2 (TGase 2), or tissue transglutaminase, catalyzes either epsilon-(gamma-glutamyl)lysine or N(1), N(8)-(gamma-glutamyl)spermidine isopeptide bonds [19].
• The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression [12].
• Identification of a novel recognition sequence for fibronectin within the NH2-terminal beta-sandwich domain of tissue transglutaminase [13].
• The relative abundance of tissue transglutaminase increased 3-4-fold after 6 or 24 h of culture with either concentration of 4-hydroperoxycyclophosphamide; immunoreactive protein in drug-treated limbs decreased to control levels by 48 h [20].

Physical interactions of Tgm2

• Identification of the fibronectin-binding site on tissue transglutaminase will help to dissect the role of this protein in cell-matrix interactions [13].

Enzymatic interactions of Tgm2

• Tissue transglutaminase (tTG) is a multifunctional enzyme that catalyzes both transamidation and GTPase reactions [15].

Co-localisations of Tgm2

• We now show by confocal microscopy that tTG colocalizes with pericellular fibronectin in these cells, and by immunogold electron microscopy that the two proteins are found in clusters at the cell surface [21].

Regulatory relationships of Tgm2

• Studying transiently co-transfected elements of the mouse tissue transglutaminase promoter linked to a reporter enzyme revealed their overall repression in cells expressing c-Myc [22].
• Tissue transglutaminase triggers oligomerization and activation of dual leucine zipper-bearing kinase in calphostin C-treated cells to facilitate apoptosis [23].

Other interactions of Tgm2

• The purpose of this study was to investigate the relationship between the occurrence of apoptosis in the mouse limb during normal and abnormal development as well as the expression of tissue transglutaminase and clusterin, two proteins associated with apoptotic cell death [20].
• Experiments with deletion mutants of the first domain revealed that amino acids 81-140 of tissue transglutaminase are involved in fibronectin binding [13].
• Analysis of Ras/Raf downstream signaling with specific pharmacological inhibitors reveals that the decrease in tTG expression is mediated by the p38 MAPK, c-Jun NH2-terminal kinase, and phosphatidylinositol 3-kinase pathways [14].
• Substitution of individual domains of tissue transglutaminase with those from homologous factor XIIIA showed that the major fibronectin-binding site is present within the first beta-sandwich domain of the protein [13].
• In this second model of cell wounding, redistribution of tTG activity to the extracellular matrix was also demonstrated, an effect which may serve to stabilize tissues post-trauma, and thus contribute to the maintenance of tissue integrity [24].

Analytical, diagnostic and therapeutic context of Tgm2

• RT-PCR analysis demonstrated that tTG mRNA content increases during mouse forebrain development, whereas immunoblot analysis demonstrated that tTG protein content decreases during this time [15].
• Using these cells, loss of Ca(2+) homoeostasis following electroporation led to a tTG-dependent formation of highly cross-linked proteinaceous shells from intracellular proteins [24].
• We have investigated whether arachidonic acid could regulate tissue transglutaminase (tTGase) via intracellular reactive oxygen species (ROS) in NIH3T3 cells. tTGase was identified in NIH3T3 cells by Western blot and confocal microscopy [25].
• The whole-body gamma-irradiated mouse ovaries were collected and immunohistochemistry for tTG and in situ 3'-end labeling (TUNEL) was performed [26].
• Based on the identification of atretic follicles with hematoxylin-eosin and TUNEL immunostaining, tTG expression was evaluated and compared between normal (NF) and atretic follicles (AF) [26].

References