Transglutaminases in disease

Kim, Soo Youl; Jeitner, Thomas M.; Steinert, Peter M.

doi:10.1016/s0197-0186(01)00064-x

Cited by 144 publications

(107 citation statements)

References 208 publications

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“…The tTG-catalyzed posttranslational modification of the substrate proteins, either by polymerization or by covalent linkage to soluble low molecular weight molecules such as amines or peptides, can alter the physical-chemical characteristics of the substrates, thus playing a key role in modulating their biological activity. However, in some circumstances, tTG-catalyzed post-translational mod- ifications of proteins may generate auto-antibodies as it happens in auto-immune disorders such as CD (14). Such a phenomenon was explained by a mechanism where tTG, acting as a hapten in the generation of antibodies against gliadin and itself, catalyzes the synthesis of heteromeric gliadin-tTG complexes.…”

Section: Discussionmentioning

confidence: 99%

“…Latent transforming growth factor-␤ that is considered the major autocrine/paracrine inhibitory regulator in the intestinal epithelium is activated by tTG (13). Finally, tTG-mediated post-translational modifications of proteins may represent pathogenic mechanisms in diseases, including celiac disease (CD) (14). CD is an autoimmune pathology triggered in genetically predisposed patients by exposure to gliadin, a flour protein, thus evoking local immune reactions and mucosal atrophy (15).…”

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confidence: 99%

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Proteomics Identification of Acyl-acceptor and Acyl-donor Substrates for Transglutaminase in a Human Intestinal Epithelial Cell Line

Orrú

Caputo

D’Amato

et al. 2003

Journal of Biological Chemistry

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Transglutaminase (TG)-catalyzed cross-linking of both intracellular and extracellular proteins is an important biochemical event. However, increased concentrations of cross-linked proteins have been observed in many disorders. Moreover, TG-catalyzed modification of proteins might generate new self-antigens responsible for the autoimmune response, as in celiac disease. The identification of available substrates may offer an understanding of how the TG-catalyzed post-translational modification has an impact on physiology and disease. We used a proteomic approach to identify TG-modified protein targets in human intestinal epithelial cells to determine the extent to which transglutaminase specifically contributes to celiac disease. Two probes were used for endogenous TG activity: 5-(biotinamido)pentylamine, which represents the acyl-acceptor, and a biotinylated glutamine-containing peptide, which represents the acyl-donor. This approach identified >25 proteins, which range from 30,000 to 300,000 Daltons and can serve as acyl-acceptor and/or acyl-donor for transglutaminase. Some of them were known transglutaminase substrates, whereas others had not been previously identified. These targets include proteins involved in cytoskeletal network organization, folding of proteins, transport processes, and miscellaneous metabolic functions.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Proteomics Identification of Acyl-acceptor and Acyl-donor Substrates for Transglutaminase in a Human Intestinal Epithelial Cell Line

Orrú

Caputo

D’Amato

et al. 2003

Journal of Biological Chemistry

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“…TG2 has been implicated in several autoimmune diseases (82). A variety of TG2 substrates have been identified as autoantigens in autoimmune diseases.…”

Section: Role Of Transglutaminases In Inflammationmentioning

confidence: 99%

“…The mechanism by which TG2 might contribute to autoimmunity is unclear. In the case of celiac disease, TG2 is thought to generate neoepitopes from gliadin through deamidation of some of the glutamine residues that constitute 40% of the amino acids residues of this molecule (82). TG2 also cross links itself to gliadin, a process that appears to foster the generation of anti-gliadin and anti-TG2 antibodies (82).…”

Section: Role Of Transglutaminases In Inflammationmentioning

confidence: 99%

Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

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All transglutaminases share the common enzymatic activity of transamidation, or the cross-linking of glutamine and lysine residues to form N epsilon (gamma-glutamyl) lysyl isopeptide bonds. The plasma proenzyme factor XIII is responsible for stabilizing the fibrin clot against physical and fibrinolytic disruption. Another member of the transglutaminase family, tissue transglutaminase or TG2 is abundantly expressed in cardiomyocytes, vascular cells and macrophages. The transglutaminases have a variety of functions independent of their transamidating activity. For example, TG2 binds and hydrolyzes GTP, thereby fostering signal transduction by several G protein coupled receptors. Accumulating evidence points to novel roles for factor XIII and TG2 in cardiovascular biology including: (a) modulating platelet activity, (b) regulating glucose control, (c) contributing to the development of hypertension, (d) influencing the progression of atherosclerosis, (e) regulating vascular permeability and angiogenesis (f) and contributing to myocardial signaling, contractile activity and ischemia/reperfusion injury. In this review, we summarize the cardiovascular biology of two members of the family of transglutaminases, Factor XIII and TG2.

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“…The aberrant induction of TG2 activity contributes to various pathologies, including neurodegenerative diseases, atherosclerosis, autoimmune diseases, and fibrosis (Kim et al 2002;Szondy et al 2011). Also, studies on plant TGases and their application in material science and as potential biotechnological tool kits are included.…”

Section: Editorialmentioning

confidence: 99%

Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives

Agostinelli

2014

Amino Acids

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Transglutaminases in disease

Cited by 144 publications

References 208 publications

Proteomics Identification of Acyl-acceptor and Acyl-donor Substrates for Transglutaminase in a Human Intestinal Epithelial Cell Line

Proteomics Identification of Acyl-acceptor and Acyl-donor Substrates for Transglutaminase in a Human Intestinal Epithelial Cell Line

Roles of transglutaminases in cardiac and vascular diseases

Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives

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