Potential of transglutaminase 2 as a therapeutic target

Expert Opinion on Therapeutic Targets

Volumn 14, Issue 9, 2010, Pages 989-1003

  Caccamo, Daniela ^a   Currò, Monica ^a   Ientile, Riccardo ^a  

^a UNIVERSITY OF MESSINA   (Italy)

Author keywords

Cancer; Celiac disease; Fibrosis; Inhibitors; Neurodegenerative disorders; Transglutaminase

Indexed keywords

1,3 DIMETHYL 2 [(OXOPROPYL)THIO]IMIDAZOLIUM; 2 [(2 OXOPROPYL)THIO]IMIDAZOLIUM; 5 (BIOTINAMIDO)PENTYLAMINE; ACYLTRANSFERASE INHIBITOR; CYSTAMINE; DANSYLCADAVERINE; KCC 009; N BENZYLOXYCARBONYL PHENYLALANYL 6 DIMETHYL SULPHONIUM 5 OXO NORLEUCINE; NORLEUCINE; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE 2; PUTRESCINE; QUINOLINE CARBINOLINIC 5 FLUOROTRYPTOPHANHALO DIHYDROISOXAZOLE; R 281; R 283; THIOMIDAZIOLIUM; UNCLASSIFIED DRUG;

AUTOIMMUNE DISEASE; CELIAC DISEASE; CELL CULTURE; CLINICAL TRIAL; DEAMINATION; DEGENERATIVE DISEASE; ENZYME ACTIVITY; ENZYME INHIBITION; GLIOBLASTOMA; HUMAN; IN VIVO STUDY; INFLAMMATORY DISEASE; KIDNEY FIBROSIS; NEOPLASM; NONHUMAN; PATHOGENESIS; PROTEIN CROSS LINKING; REVIEW;

ANIMALS; CALCIUM; DRUG DELIVERY SYSTEMS; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GTP-BINDING PROTEINS; HUMANS; TRANSGLUTAMINASES;

EID: 77955455920     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.2010.510134     Document Type: Review

References (99)

1. Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. Biochem J 2002;368:377-396 (Pubitemid 35454517)
2. Iismaa SE, Mearns BM, Lorand L, et al Transglutaminases and disease: lessons from genetically engineered mouse models and inherited disorders. Physiol Rev 2009;89:991-1023
3. Park D, Choi SS, Ha KS. Transglutaminase 2: a multi-functional protein in multiple subcellular compartments. Amino Acids 2010;39:619-631
4. Esposito C, Caputo I, Troncone R. New therapeutic strategies for coeliac disease: tissue transglutaminase as a target. Curr Med Chem 2007;14:2572-80 (Pubitemid 350018470)
5. Kim SY. Transglutaminase 2 in inflammation. Front Biosci 2006;11:3026-35
6. Ruan Q, Johnson GV. Transglutaminase 2 in neurodegenerative disorders. Front Biosci 2007;12:891-904 (Pubitemid 46846864)
7. Mangala LS, Mehta K. Tissue transglutaminase (TG2) in cancer biology. Prog Exp Tumor Res 2005;38:125-38 (Pubitemid 40301046)
8. Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 2002;27:534-539 (Pubitemid 35279599)
9. Esposito C, Caputo I. Mammalian transglutaminases. Identification of substrates as a key to physiological function and physiopathological relevance. FEBS J 2005;272:615-631 (Pubitemid 40208867)
10. Case A, Stein RL. Kinetic analysis of the action of tissue transglutaminase on peptide and protein substrates. Biochemistry 2003;42:9466-9481 (Pubitemid 36959255)
11. Smethurst PA, Griffin M. Measurement of tissue transglutaminase activity in a permeabilized cell system: its regulation by Ca2+ and nucleotides. Biochem J 1996;313:803-808 (Pubitemid 26050811)
12. Zhang J, Lesort M, Guttmann RP, Johnson GVW. Modulation of the in situ activity of tissue transglutaminase by calcium and GTP. J Biol Chem 1998;273:2288-2295 (Pubitemid 28069282)
13. Nicholas B, Smethurst P, Verderio E, et al. Cross-linking of cellular proteins by tissue transglutaminase during necrotic cell death: a mechanism for maintaining tissue integrity. Biochem J 2003;371:413-422 (Pubitemid 36547624)
14. Balklava Z, Verderio E, Collighan R, et al. Analysis of tissue transglutaminase function in the migration of Swiss 3T3 fibroblasts: the active-state conformation of the enzyme does not affect cell motility but is important for its secretion. J Biol Chem 2002;277(19):16567-16575 (Pubitemid 34967673)
15. Zemskov EA, Janiak A, Hang J, et al. The role of tissue transglutaminase in cell- matrix interactions. Front Biosci 2006;11:1057-1076 (Pubitemid 43253460)
16. Facchiano F, Facchiano A, Facchiano AM. The role of transglutaminase-2 and its substrates in human diseases. Front Biosci 2006;11:1758-1773 (Pubitemid 43253392)
17. De Vivo G, Martin A, Trotta T, Gentile V. Role of transglutaminase- catalyzed reactions in the post-translational modifications of proteins responsible for immunological disorders. Inflamm Allergy Drug Targets 2008;7:24-29 (Pubitemid 351663642)
18. Gentile V, Cooper AJ. Transglutaminases-possible drug targets in human diseases. Curr Drug Targets CNS Neurol Disord 2004;3:99-104 (Pubitemid 38854904)
19. Wodzinska JM. Transglutaminases as targets for pharmacological inhibition. Mini Rev Med Chem 2005;5:279-292
20. Esposito C, Paparo F, Caputo I, et al. Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ. Gut 2002;51:177-181 (Pubitemid 34791442)
21. Muma NA. Transglutaminase is linked to neurodegenerative diseases. J Neuropathol Exp Neurol 2007;66:258-263
22. Jellinger KA. Recent advances in our understanding of neurodegeneration. J Neural Transm 2009;116:1111-1162
23. Jeitner TM, Pinto JT, Krasnikov BF, et al. Transglutaminases and neurodegeneration. J Neurochem 2009;109:160-166
24. Wilhelmus MMM, van Dam AM, Drukarch B. Tissue transglutaminase: a novel pharmacological target aggregation in preventing toxic protein aggregation in neurodegenerative diseases. Eur J Pharmacol 2008;585:464-472
25. AbdAlla S, Lother H, el Missiry A, et al. Angiotensin II AT2 receptor oligomers mediate G-protein dysfunction in an animal model of Alzheimer Disease. J Biol Chem 2009;284:6554-6565
26. Junn E, Ronchetti RD, Quezado MM, et al. Tissue transglutaminase-induced aggregation of alpha-synuclein: implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 2003;100:2047-2052 (Pubitemid 36254571)
27. Lai TS, Tucker T, Burke JR, et al. Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats. J Neurochem 2004;88:1253-1260 (Pubitemid 38280693)
28. Mastroberardino PG, Iannicola C, Nardacci R, et al. 'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ 2002;9:873-880 (Pubitemid 35023603)
29. Bailey CD, Johnson GV. Tissue transglutaminase contributes to disease progression in the R6/2 Huntington's disease mouse model via aggregate independent mechanisms. J Neurochem 2005;92:83-92
30. Jeitner TM, Delikatny EJ, Ahlqvist J, et al. Mechanism for the inhibition of transglutaminase 2 by cystamine. Biochem Pharmacol 2005;69:961-970 (Pubitemid 40312713)
31. Dedeoglu A, Kubilus JK, Jeitner TM, et al. Therapeutic effects of cystamine in a murine model of Huntington's disease. J Neurosci 2002;22:8942-8950 (Pubitemid 35379064)
32. Van Raamsdonk JM, Pearson J, Bailey CD, et al. Cystamine treatment is neuroprotective in theYAC128 mouse model of Huntington disease. J Neurochem 2005;95:210-220 (Pubitemid 41384439)
33. Stack EC, Ferro JL, Kim J, et al. Therapeutic attenuation of mitochondrial dysfunction and oxidative stress in neurotoxin models of Parkinson's disease. Biochim Biophys Acta 2008;1782:151-162
34. Igarashi S, Koide R, Shimohata T, et al. Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nat Genet 1998;18:111-117 (Pubitemid 28082456)
35. de Cristofaro T, Affaitati A, Cariello L, et al. The length of polyglutamine tract, its level of expression, the rate of degradation, and the transglutaminase activity influence the formation of intracellular aggregates. Biochem Biophys Res Commun 1999;260:150-158 (Pubitemid 29351800)
36. Beck KA, De Girolamo LA, Griffin M, Billett EE. The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells. Neurosci Lett 2006;405:46-51 (Pubitemid 44142827)
37. Karpuj MV, Becher MW, Springer JE, et al. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med 2002;8:143-149
38. Ientile R, Campisi A, Raciti G, et al. Cystamine inhibits transglutaminase and caspase-3 cleavage in glutamate-exposed astroglial cells. J Neurosci Res 2003;74:52-59 (Pubitemid 37176666)
39. Siegel M, Khosla C. Transglutaminase 2 inhibitors and their therapeutic role in disease states. Pharmacol Ther 2007;115:232-245 (Pubitemid 47042912)
40. Dudek NL, Dai Y, Muma NA. Neuroprotective effects of calmodulin peptide 76-121aa: disruption of calmodulin binding to mutant huntingtin. Brain Pathol 2008;20:176-189 (Pubitemid 351507490)
41. Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 2009;137:1912-1933
42. Dietrich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801 (Pubitemid 27298728)
43. Arentz-Hansen H, Mc Adam S, Molberg O, et al. Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues. Gastroenterology 2003;123:803-809 (Pubitemid 34977086)
44. Qiao SW, Piper J, Haraldsen G, et al. Tissue transglutaminase-mediated formation and cleavage of histamine-gliadin complexes: biological effects and implications for celiac disease. J Immunol 2005;174:1657-1663
45. Molberg O, McAdam S, Lundin KE, et al. T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase. Eur J Immunol 2001;31:1317-1323 (Pubitemid 32454680)
46. Arentz-Hansen H, Korner R, Molberg O, et al. The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med 2000;191:603-612
47. Torres MI, Lopez Casado MA, Rios A. New aspects in celiac disease. World J Gastroenterol 2007;13:1156-1161 (Pubitemid 46592954)
48. Korponay-Szabo IR, Vecsei Z, Kiraly R, et al. Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize. J Pediatr Gastroenterol Nutr 2008;46:253-261
49. Mowat AM. Coeliac disease-a meeting point for genetics, immunology, and protein chemistry. Lancet 2003;361:1290-1292
50. Vader W, Kooy Y, Van Veelen P, et al. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 2002;122:1729-1737 (Pubitemid 34651415)
51. Villalta D, Tonutti E, Prause C, et al. IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency. Clin Chem 2010;56:464-468
52. Dolfini E, Roncoroni L, Elli L, et al. Cytoskeleton reorganization and ultrastructural damage induced by gliadin in a three-dimensional in vitro model. World J Gastroenterol 2005;11:7597-7601 (Pubitemid 43168422)
53. Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci USA 2009;106:15849-15854
54. Daynes RAD, Jones C. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2002;2:748-759
55. Maiuri L, Luciani A, Villella VR, et al. Lysosomal accumulation of gliadin p31-43 peptide induces oxidative stress and tissue transglutaminase- mediated PPARgamma downregulation in intestinal epithelial cells and coeliac mucosa. Gut 2010;59:311-319
56. Maiuri L, Ciacci C, Ricciardelli I, et al. Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology 2005;129:1400-1413 (Pubitemid 41597382)
57. Choi K, Siegel M, Piper JL, et al. Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2. Chem Biol 2005;12:469-475 (Pubitemid 40588922)
58. Watts RE, Siegel M, Khosla C. Structure- activity relationship analysis of the selective inhibition of transglutaminase 2 by dihydroisoxazoles. J Med Chem 2006;49:7493-7501 (Pubitemid 44913408)
59. Hausch F, Halttunen T, Maki M, Khosla C. Design, synthesis, and evaluation of gluten peptide analogs as selective inhibitors of human tissue transglutaminase. Chem Biol 2003;10:225-231 (Pubitemid 36380279)
60. Reed GL, Lukacova D. Generation and mechanism of action of a potent inhibitor of factor XIII function. Thromb Haemost 1995;74:680-685
61. Barone MV, Caputo I, Ribecco MT, et al. Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease. Gastroenterology 2007;132:1245-1253 (Pubitemid 46627567)
62. Herman JF, Mangala LS, Mehta K. Implications of increased tissue transglutaminase (TG2) expression in drug-resistant breast cancer (MCF-7) cells. Oncogene 2006;25:3049-3058 (Pubitemid 43780469)
63. Kotsakis P, Griffin M. Tissue transglutaminase in tumour progression: friend or foe? Amino Acids 2007;33:373-384 (Pubitemid 47222962)
64. Chhabra A, Verma A, Mehta K. Tissue transglutaminase promotes or suppresses tumors depending on cell context. Anticancer Res 2009;29:1909-1919
65. Kang SK, Kim YS, Kong YJ, et al. Disialoganglioside GD3 synthase expression recruits membrane transglutaminase 2 during erythroid differentiation of the human chronic myelogenous leukemia K562 cells. Proteomics 2008;8:3317-3328
66. Mehta K, Fok J, Miller FR, et al. Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer. Clin Cancer Res 2004;10:8068-8076 (Pubitemid 39587548)
67. Kim DS, Park KS, Kim SY. Silencing of TGase 2 sensitizes breast cancer cells to apoptosis by regulation of survival factors. Front Biosci 2009;14:2514-2521
68. Joshi S, Guleria R, Pan J, et al. Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells. Oncogene 2006;25:240-247 (Pubitemid 43083685)
69. Mangala LS, Fok JY, Zorrilla-Calancha IR, et al. Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells. Oncogene 2007;26:2459-2470 (Pubitemid 46597265)
70. Verma A, Wang H, Manavathi B, et al. Increased expression of tissue transglutaminase in pancreatic ductal adenocarcinoma and its implications in drug resistance and metastasis. Cancer Res 2006;66:10525-10533 (Pubitemid 44799775)
71. Antonyak MAA, Miller M, Jansen JM, et al. Augmentation of tissue transglutaminase expression and activation by epidermal growth factor inhibit doxorubicin-induced apoptosis in human breast cancer cells. J Biol Chem 2004;279:41461-41467
72. Birckbichler PJ, Bonner RB, Hurst RE, et al. Loss of tissue transglutaminase as a biomarker for prostate adenocarcinoma. Cancer 2000;89:412-423 (Pubitemid 30489892)
73. Mann AP, Verma A, Sethi G, et al. Overexpression of tissue transglutaminase leads to constitutive activation of nuclear factor-kappaB in cancer cells: delineation of a novel pathway. Cancer Res 2006;66:8788-8795 (Pubitemid 44449196)
74. Yuan L, Choi K, Khosla C, et al. Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas. Mol Cancer Ther 2005;4:1293-1302
75. Collighan RJ, Griffin M. Transglutaminase 2 cross-linking of matrix proteins: biological significance and medical applications. Amino Acids 2009;36:659-670
76. Fisher M, Jones RA, Huang L, et al. Modulation of tissue transglutaminase in tubular epithelial cells alters extracellular matrix levels: a potential mechanism of tissue scarring. Matrix Biol 2009;28:20-31
77. Shweke N, Boulos N, Jouanneau C, et al. Tissue transglutaminase contributes to interstitial renal fibrosis by favoring accumulation of fibrillar collagen through TGF-beta activation and cell infiltration. Am J Pathol 2008;173:631-642
78. Griffin M, Mongeot A, Collighan R, et al. Synthesis of potent water-soluble tissue transglutaminase inhibitors. Bioorg Med Chem Lett 2008;18:5559-5562
79. Johnson TS, Fisher M, Haylor JL, et al. Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease. J Am Soc Nephrol 2007;18:3078-3088 (Pubitemid 350223968)
80. Huang L, Haylor JL, Hau Z, et al. Transglutaminase inhibition ameliorates experimental diabetic nephropathy. Kidney Int 2009;76:383-394
81. Linge C, Richardson J, Vigor C, et al. Hypertrophic scar cells fail to undergo a form of apoptosis specific to contractile collagen-the role of tissue transglutaminase. J Invest Dermatol 2005;125:72-82 (Pubitemid 40981426)
82. Parsons AC, Yosipovitch G, Sheehan DJ, et al. Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol 2007;29:433-6 (Pubitemid 47463850)
83. Sane DC, Kontos JL, Greenberg CS. Roles of transglutaminases in cardiac and vascular diseases. Front Biosci 2007;12:2530-2545
84. Tatsukawa H, Kojima S. Recent advances in understanding the roles of transglutaminase 2 in alcoholic steatohepatitis. Cell Biol Int 2010;34:325-334
85. Sarang Z, Toth B, Balajthy Z, et al. Some lessons from the tissue transglutaminase knockout mouse. Amino Acids 2009;36:625-31
86. Elli L, Bergamini CM, Bardella MT, et al. Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver. Dig Liver Dis 2009;41:541-550
87. Jeitner TM, Muma NA, Battaile KP, Cooper AJ. Transglutaminase activation in neurodegenerative diseases. Future Neurol 2009;4:449-467
88. Caputo I, Barone MV, Martucciello S, et al. Tissue transglutaminase in celiac disease: role of autoantibodies. Amino Acids 2009;36:693-9
89. Harrison CA, Layton CM, Hau Z, et al. Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin. Br J Dermatol 2007;156:247-257 (Pubitemid 46095951)
90. Fesus L, Szondy Z. Transglutaminase 2 in the balance of cell death and survival. FEBS Lett 2005;579:3297-3302 (Pubitemid 40804677)
91. Ientile R, Caccamo D, Griffin M. Tissue transglutaminase and the stress response. Amino Acids 2007;33:385-394 (Pubitemid 47222963)
92. Lai TS, Davies C, Greenberg CS. Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation. Protein Sci 2010;19:229-235
93. Lai TS, Liu Y, Tucker T, et al. Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem Biol 2008;15:969-978
94. Szondy Z, Sarang Z, Molnar P, et al. Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. Proc Natl Acad Sci USA 2003;100(13):7812-7817 (Pubitemid 36760052)
95. Bernassola F, Federici M, Corazzari M, et al. Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. FASEB J 2002;16:1371-1378 (Pubitemid 34913309)
96. Battaglia G, Farrace MG, Mastroberardino PG, et al. Transglutaminase 2 ablation leads to defective function of mitochondrial respiratory complex I affecting neuronal vulnerability in experimental models of extrapyramidal disorders. J Neurochem 2007;100:36-49 (Pubitemid 46090773)
97. Candi E, Oddi S, Paradisi A, et al. Expression of transglutaminase 5 in normal and pathologic human epidermis. J Invest Dermatol 2002;119:670-677
98. Davies G, Ablin RJ, Mason MD, et al. Expression of the prostate transglutaminase (TGase-4) in prostate cancer cells and its impact on the invasiveness of prostate cancer. J Exp Ther Oncol 2007;6:257-264 (Pubitemid 46789726)
99. Sohn J, Kim TI, Yoon YH, et al. Novel transglutaminase inhibitors reverse the inflammation of allergic conjunctivitis. J Clin Invest 2003;111:121-128 (Pubitemid 36134855)