Preface
This is the third special issue focused on “Transglutaminases” that is now available on this journal and dedicated to one of the pioneers of these enzymes, John Edward Folk, who died December 2010 [see in this issue Beninati et al. 2012a]. The first edition, “Polyamines and Transglutaminases” was published in Amino Acids, vol 26, no. 4, 2004, with the contribution of two prestigious Guest Editors as Alberto Abbruzzese and Mauro Piacentini. This editorial initiative was followed by the second special issue published in occasion of the 50th years of the discovery of transglutaminase. Indeed, “Transglutaminase 2: 50th Anniversary of the Discovery” Amino Acids, vol 36, no. 4, 2009, was published with the valuable collaboration of Carlo Maria Bergamini and Mauro Piacentini (Beninati et al. 2009). To continue with this editorial tradition, on this occasion, an outstanding board of Guest Editors composed by Francesco Facchiano and Mauro Piacentini has also been invited to promote this initiative and recruit a selected panel of Authors, many of who participated in the first and second edition of the Gordon Conference on Transglutaminases: “Transglutaminases in Human Diseases Processes” chaired by Rickard L Eckert and Kapil Mehta on July 18–23, 2010, and by Kapil Mehta and Mauro Piacentini on July 15–20, 2012, held at Davidson College, NC, USA. In this Amino Acids special issue, the manuscripts were selected to reflect the progress and the future perspectives of transglutaminases.
Similar content being viewed by others
References
Abe S, Yamashita K, Kohno H, Ohkubo Y (2000) Involvement of transglutaminase in the receptor-mediated endocytosis of mouse peritoneal macrophages. Biol Pharm Bull 23:1511–1513
Akimov SS, Krylov D, Fleischman LF, Belkin AM (2000) Tissue transglutaminase is an integrin-binding adhesion co-receptor for fibronectin. J Cell Biol 148:825–838
Al-Jallad HF, Nakano Y, Chen JL, McMillan E, Lefebvre C, Kaartinen MT (2006) Transglutaminase activity regulates osteoblast differentiation and matrix mineralization in MC3T3-E1 osteoblast cultures. Matrix Biol 25:135–148
Antonyak MA, Jansen JM, Miller AM, Ly TK, Endo M, Cerione RA (2006) Two isoforms of tissue transglutaminase mediate opposing cellular fates. Proc Natl Acad Sci USA 103:18609–18614
Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161
Badarau E, Collighan RJ, Griffin M (2011) Recent advances in the development of tissue transglutaminase (TG2) inhibitors. Amino Acids. doi:10.1007/s00726-011-1188-4
Bakker EN, Pistea A, VanBavel E (2008) Transglutaminases in vascular biology: relevance for vascular remodeling and atherosclerosis J Vasc Res. 45:271–278
Beninati S, Nicolini L, Jakus J, Passeggio A, Abbruzzese A (1995) Identification of a substrate site for transglutaminases on the human protein synthesis initiation factor 5A. Biochem J 305:725–728
Beninati S, Gentile V, Caraglia M, Lentini A, Tagliaferri P, Abbruzzese A (1998) Tissue transglutaminase expression affects hypusine metabolism in BALB/c 3T3 cells. FEBS Lett 437:34–38
Beninati S, Bergamini CM, Piacentini M (2009) An overview of the first 50 years of transglutaminase research. Amino Acids 36:591–598
Beninati S, Park MH, Wolff E, Fésüs L, Abbruzzese A, Chung SI, Carmassi F, Cocuzzi E, Trawick ML, Piacentini M (2012a) In memoriam: John E. Folk (1925–2010). Amino Acids Doi:10.1007/s00726-012-1367-y
Beninati S, Iorio RA, Tasco G, Serafini-Fracassini D, Casadio R, Del Duca S (2012b) Expression of different forms of transglutaminases by immature cells of Helianthus tuberosus sprout apices. Amino Acids. doi:10.1007/s00726-012-1411-y
Bergamini CM, Signorini M, Barbato R, Menabò R, Di Lisa F, Gorza L, Beninati S (1995) Transglutaminase-catalyzed polymerization of troponin in vitro. Biochem Biophys Res Commun 206:201–206
Bissell MJ (1999) Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch. A rose by any other name? Am J Pathol 155:675–679
Bock SA, Atkins FM (1990) Patterns of food hypersensitivity during sixteen years of double-blind, placebo-controlled food challenges. J Pediatr 117:561–567
Boehm JE, Singh U, Combs C, Antonyak MA, Cerione RA (2002) Tissue transglutaminase protects against apoptosis by modifying the tumor suppressor protein p110 Rb. J Biol Chem 277:20127–20130
Bowser TE, Trawick ML (2011) Probing the specificity of gamma-glutamylamine cyclotransferase: an enzyme involved in the metabolism of transglutaminase-catalyzed protein crosslinks. Amino Acids. doi:10.1007/s00726-011-1153-2
Budillon A, Carbone C, Di Gennaro E (2011) Tissue transglutaminase: a new target to reverse cancer drug resistance. Amino Acids. doi:10.1007/s00726-011-1167-9
Caccamo D, Condello S, Ferlazzo N, Currò M, Griffin M, Ientile R (2011) Transglutaminase 2 interaction with small heat shock proteins mediate cell survival upon excitotoxic stress. Amino Acids. doi:10.1007/s00726-011-1083-z
Caputo I, Lepretti M, Secondo A, Martucciello S, Paolella G, Sblattero D, Barone MV, Esposito C (2011) Anti-tissue transglutaminase antibodies activate intracellular tissue transglutaminase by modulating cytosolic Ca(2+) homeostasis. Amino Acids. doi:10.1007/s00726-011-1120-y
Caraglia M, Tagliaferri P, Budillon A, Abbruzzese A (1999) Post-translational modifications of eukaryotic initiation factor-5A (eIF-5A) as a new target for anti-cancer therapy. Adv Exp Med Biol 472:187–198
Caraglia M, Park MH, Wolff EC, Marra M, Abbruzzese A (2011) eIF5A isoforms and cancer: two brothers for two functions? Amino Acids. doi:10.1007/s00726-011-1182-x
Chhabra A, Verma A, Mehta K (2009) Tissue transglutaminase promotes or suppresses tumors depending on cell context. Anticancer Res 29:1909–1919
Citron BA, SantaCruz KS, Davies PJ, Festoff BW (2001) Intron–exon swapping of transglutaminase mRNA and neuronal Tau aggregation in Alzheimer’s disease. J Biol Chem 276:3295–3301
Dardik R, Loscalzo J, Eskaraev R, Inbal A (2005) Molecular mechanisms underlying the proangiogenic effect of factor XIII. Arterioscler Thromb Vasc Biol 25:526–532
De Laurenzi V, Melino G (2001) Gene disruption of tissue transglutaminase. Mol Cell Biol 21:148–155
Deasey S, Shanmugasundaram S, Nurminskaya M (2011) Tissue-specific responses to loss of transglutaminase 2. Amino Acids. doi:10.1007/s00726-011-1183-9
Facchiano A, Facchiano F (2009) Transglutaminases and their substrates in biology and human diseases: 50 years of growing. Amino Acids 36:599–614
Facchiano AM, Facchiano A, Facchiano F (2003) Active sequences collection (ASC) database: a new tool to assign functions to protein sequences. Nucleic Acids Res 31:379–382
Facchiano F, Deloye F, Doussau F, Innamorati G, Ashton AC, Dolly JO, Beninati S, Facchiano A, Luini A, Poulain B, Benfenati F (2010) Transglutaminase participates in the blockade of neurotransmitter release by tetanus toxin: evidence for a novel biological function. Amino Acids 39:257–269
Facchiano F, D’Arcangelo D, Lentini A, Rossi S, Senatore C, Pannellini T, Tabolacci C, Facchiano AM, Facchiano A, Beninati S (2012) Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study. Amino Acids. doi:10.1007/s00726-012-1351-6
Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898
Fimia GM, Piacentini M (2010) Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Life Sci 67(10):1581–1588
Fink ML, Folk JE (1981) γ-Glutamylamine cyclotransferase. An enzyme involved in the catabolism of epsilon-(gamma-glutamyl) lysine and other gamma-glutamylamines. Mol Cell Biochem 38:59–67
Folk JE (1983) Mechanism and basis for specificity of transglutaminase catalyzed epsilon-(gamma-glutamyl) lysine bond formation. Adv Enzymol Relat Areas Mol Biol 54:1–56
Folk JE, Cole PW (1966) Mechanism of action of guinea pig liver transglutaminase. I. Purification and properties of the enzyme: identification of a functional cysteine essential for activity. J Biol Chem 241:5518–5525
Folk JE, Park MH, Chung SI, Schrode J, Lester EP, Cooper HL (1980) Polyamines as physiological substrates for transglutaminases. J Biol Chem 255:3695–3700
Forsprecher J, Wang Z, Nelea V, Kaartinen MT (2009) Enhanced osteoblast adhesion on transglutaminase 2-crosslinked fibronectin. Amino Acids 36:747–753
Garabuczi E, Kiss B, Felszeghy S, Tsay GJ, Fésüs L, Szondy Z (2011) Retinoids produced by macrophages engulfing apoptotic cells contribute to the appearance of transglutaminase 2 in apoptotic thymocytes. Amino Acids. doi:10.1007/s00726-011-1119-4
Giatromanolaki A, Sivridis E, Koukourakis MI (2004) Tumour angiogenesis: vascular growth and survival. APMIS 112:431–440
Grenard P, Bates MK, Aeschlimann D (2001) Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z. J Biol Chem 276:33066–33078
Griffin M, Casadio R, Bergamini CM (2002) Transglutaminases: nature’s biological glues. Biochem J 368:377–396
Hollier BG, Kricker JA, Van Lonkhuyzen DR, Leavesley DI, Upton Z (2008) Substrate-bound insulin-like growth factor (IGF)-I-IGF binding protein-vitronectin-stimulated breast cell migration is enhanced by coactivation of the phosphatidylinositide 3-kinase/AKT pathway by (alpha)v-integrins and the IGF-I receptor. Endocrinology 149:1075–1090
Jandu SK, Webb AK, Pak A, Sevinc B, Nyhan D, Belkin AM, Flavahan NA, Berkowitz DE, Santhanam L (2011) Nitric oxide regulates tissue transglutaminase localization and function in the vasculature. Amino Acids. doi:10.1007/s00726-011-1090-0
Jang GY, Jeon JH, Cho SY, Shin DM, Kim CW, Jeong EM, Bae HC, Kim TW, Lee SH, Choi Y, Lee DS, Park SC, Kim IG (2010) Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB activity in hypoxic tumor cells. Oncogene 29:356–367
Jeitner TM, Matson WR, Folk JE, Blass JP, Cooper AJL (2008) Increased levels of γ-Glutamyl amines in Huntington disease CSF. J Neurochem 106:37–44
Jeitner TM, Pinto JT, Krasnikov BF, Horswill M, Cooper AJL (2009) Transglutaminases and neurodegeneration. J Neurochem 109:160–166
Jeitner TM, Battaile K, Cooper AJ (2012) γ-Glutamylamines and neurodegenerative diseases. Amino Acids. doi:10.1007/s00726-011-1209-3
Jones RA, Wang Z, Dookie S, Griffin M (2012) The role of TG2 in ECV304-related vasculogenic mimicry. Amino Acids. doi:10.1007/s00726-011-1214-6
Kaartinen MT, El-Maadawy S, Räsänen NH, McKee MD (2002) Tissue transglutaminase and its substrates in bone. J Bone Miner Res 17:2161–2173
Kashyap AS, Hollier BG, Manton KJ, Satyamoorthy K, Leavesley DI, Upton Z (2011) Insulin-like growth factor-I:vitronectin complex-induced changes in gene expression effect breast cell survival and migration. Endocrinology 152:1388–1401
Kim SY, Grant P, Lee JH, Pant HC, Steinert PM (1999) Differential expression of multiple transglutaminases in human brain. Increased expression and cross-linking by transglutaminases 1 and 2 in Alzheimer’s disease. J Biol Chem 274:30715–30721
Kim SJ, Kim KH, Ahn ER, Yoo BC, Kim SY (2011) Depletion of cathepsin D by transglutaminase 2 through protein cross-linking promotes cell survival. Amino Acids. doi:10.1007/s00726-011-1089-6
Király R, Barta E, Fésüs L (2011) Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions. Amino Acids. doi:10.1007/s00726-011-1194-6
Kiss I, Rühl R, Szegezdi E, Fritzsche B, Tóth B, Pongrácz J, Perlmann T, Fésüs L, Szondy Z (2008) Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development. Eur J Immunol 38:147–155
Kumar S, Mehta K (2011) Tissue transglutaminase, inflammation, and cancer: how intimate is the relationship? Amino Acids. doi:10.1007/s00726-011-1139-0
Legate KR, Wickstrom SA, Fassler R (2009) Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev 23:397–418
Lentini A, Provenzano B, Caraglia M, Shevchenko A, Abbruzzese A, Beninati S (2008) Impairment of the metastatic activity of melanoma cells by transglutaminase-catalyzed incorporation of polyamines into laminin and matrigel. Amino Acids 34:251–256
Lentini A, Tabolacci C, Mattioli P, Provenzano B, Beninati S (2011) Spermidine delays eye lens opacification in vitro by suppressing transglutaminase-catalyzed crystallin cross-linking. Protein J 30:109–114
Lentini A, Abbruzzese A, Provenzano B, Tabolacci C, Beninati S (2012) Transglutaminases: key regulators of cancer metastasis. Amino Acids. doi:10.1007/s00726-012-1229-7
Li F, Tsien JZ (2009) Memory and the NMDA receptors. N Engl J Med 361:302–303
Liu P, Gupta N, Jing Y, Zhang H (2008) Age-related changes in polyamines in memory associated brain structures in rats. Neuroscience 155:789–796
Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–156
Mangala LS, Fok JY, Zorrilla-Calancha IR, Verma A, Mehta K (2007) Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells. Oncogene 26:2459–2470
Martin A, Giuliano A, Collaro D, De Vivo G, Sedia C, Serretiello E, Gentile V (2011) Possible involvement of transglutaminase-catalyzed reactions in the physiopathology of neurodegenerative diseases. Amino Acids. doi:10.1007/s00726-011-1081-1
McDonough JL, Arrell DK, Van Eyk JE (1999) Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. Circ Res 84:9–20
Monsonego A, Shani Y, Friedmann I, Paas Y, Eizenberg O, Schwartz M (1997) Expression of GTP-dependent and GTP-independent tissue-type transglutaminase in cytokine-treated rat brain astrocytes. J Biol Chem 272:3724–3732
Muto Y, Nouri-Aria KT, Meager A, Alexander GJ, Eddleston AL, Williams R (1988) Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 2:72–74
Nagy L, Saydak M, Shipley N, Lu S, Basilion JP, Yan ZH, Syka P, Chandraratna RA, Stein JP, Heyman RA, Davies PJ (1996) Identification and characterization of a versatile retinoid response element (retinoic acid receptor response element-retinoid X receptor response element) in the mouse tissue transglutaminase gene promoter. J Biol Chem 271:4355–4365
Nanda N, Iismaa SE, Owens WA, Husain A, Mackay F, Graham RM (2001) Targeted inactivation of Gh/tissue transglutaminase II. J Biol Chem 276:20673–20678
Nurminskaya MV, Belkin AM (2012) Cellular functions of tissue transglutaminase. Int Rev Cell Mol Biol 294:1–97
Nurminskaya M, Kaartinen MT (2006) Transglutaminases in mineralized tissues. Front Biosci 11:1591–1606
Panteghini M (2009) Assay-related issues in the measurement of cardiac troponins. Clin Chim Acta 402:88–93
Park SS, Kim JM, Kim DS, Kim IH, Kim SY (2006) Transglutaminase 2 mediates polymer formation of I-kappaBalpha through C-terminal glutamine cluster. J Biol Chem 281:34965–34972
Perez Alea M, Thomas V, Martin G, El Alaoui S (2011) Identification of human salivary transglutaminases. Amino Acids. doi:10.1007/s00726-011-1142-5
Phatak VM, Croft SM, Rameshaiah Setty SG, Scarpellini A, Hughes DC, Rees R, McArdle S, Verderio EA (2011) Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative slicing in cancer. Amino Acids. doi:10.1007/s00726-011-1127-4
Pinkas DM, Strop P, Brunger AT, Khosla C (2007) Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol 25:2788–2796
Porta R, Giosafatto CV, di Pierro P, Sorrentino A, Mariniello L (2011) Transglutaminase-mediated modification of ovomucoid: effects on its trypsin inhibitory activity and antigenic properties. Amino Acids. doi:10.1007/s00726-011-1155-0
Quarles LD, Yohay DA, Lever LW, Caton R, Wenstrup RJ (1992) Distinct proliferative and differentiated stages of murine MC-3T3-E1 culture; an in vitro model of osteoblast development. J Bone Miner Res 7:683–692
Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G et al (2010) Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468:824–828
Ritter SJ, Davies PJ (1998) Identification of a transforming growth factor-beta1/bone morphogenetic protein 4 (TGF-beta1/BMP4) response element within the mouse tissue transglutaminase gene promoter. J Biol Chem 273(21):12798–12806
Sane DC, Kontos JL, Greenberg CS (2007) Roles of transglutaminases in cardiac and vascular diseases. Front Biosci 12:2530–2545
Santhanam L, Tuday EC, Webb AK, Dowzicky P, Kim JH, Oh YJ, Sikka G, Kuo M, Halushka MK, Macgregor AM, Dunn J, Gutbrod S, Yin D, Shoukas A, Nyhan D, Flavahan NA, Belkin AM, Berkowitz DE (2010) Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness. Circ Res 107:117–125
Sarkar NK, Clarke DD, Waelsch H (1957) An enzymically catalyzed incorporation of amines into proteins. Biochim Biophys Acta 25:451–452
Serafini-Fracassini D, Del Duca S, Beninati S (1995) Plant transglutaminases. Phytochemistry 40:355–365
Siefring GE Jr, Apostol AB, Velasco PT, Lorand L (1978) Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes. Biochemistry 17:2598–2604
Sivaramakrishnan M, Shooter GK, Upton Z, Croll TI (2011) Transglutaminases and receptor tyrosine kinases. Amino Acids. doi:10.1007/s00726-011-1113-x
Sollid LM, Jabri B (2011) Celiac disease and transglutaminase 2: a model for posttranslational modification of antigens and HLA association in the pathogenesis of autoimmune disorders. Curr Opin Immunol 23:732–738
Squerzanti M, Cervellati C, Ura B, Mischiati C, Pucci P, Annunziata S, Iannone C, Casadio R, Bergamini CM, Esposito C (2011) The side chain of glutamine 13 is the acyl-donor amino acid modified by type 2 transglutaminase in subunit T of the native rabbit skeletal muscle troponin complex. Amino Acids. doi:10.1007/s00726-011-1144-3
Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS (2012) Treatment-induced damage to the microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med. doi:10.1038/nm.2890
Szondy Z, Sarang Z, Molnar P, Nemeth T, Piacentini M, Mastroberardino PG, Falasca L, Aeschlimann D, Kovacs J, Kiss I, Szegezdi E, Lakos G, Rajnavolgyi E, Birckbichler PJ, Melino G, Fesus L (2003) Transglutaminase 2−/− mice reveal a phagocytosis associated crosstalk between macrophages and apoptotic cells. Proc Natl Acad Sci USA 100:7812–7817
Tabolacci C, Lentini A, Provenzano B, Beninati S (2012) Evidences for a role of protein cross-links in transglutaminase-related disease. Amino Acids 42:975–986
Tarantino U, Ferlosio A, Arcuri G, Spagnoli LG, Orlandi A (2011) Transglutaminase 2 as a biomarker of osteoarthritis: an update. Amino Acids. doi:10.1007/s00726-011-1181-y
Thiele CJ, Gore S, Collins S, Waxman S, Miller W (2000) Differentiate or die: the view from Montreal. Cell Death Differ 7:1014–1017
Thomas H, Beck K, Adamczyk M, Aeschlimann P, Langley M, Oita RC, Thiebach L, Hils M, Aeschlimann D (2011) Transglutaminase 6: a protein associated with central nervous system development and motor function. Amino Acids. doi:10.1007/s00726-011-1091-z
Tiboldi A, Lentini A, Provenzano B, Tabolacci C, Höger H, Beninati S, Lubec G (2012) Hippocampal polyamine levels and transglutaminase activity are paralleling spatial memory retrieval in the C57BL/6 J mouse. Hippocampus 5:1068–1074
Torricelli P, Caraglia M, Abbruzzese A, Beninati S (2011) γ-Tocopherol inhibits human prostate cancer cell proliferation by up-regulation of transglutaminase 2 and down-regulation of cyclins. Amino Acids. doi:10.1007/s00726-012-1278-y
Verma A, Mehta K (2007) Tissue transglutaminase-mediated chemoresistance in cancer cells. Drug Resist Updat 10:144–151
Watanabe K, Tsunoda K, Itoh M, Fukui M, Mori H, Hitomi K (2011) Transglutaminase 2 and Factor XIII catalyze distinct substrates in differentiating osteoblastic cell line: utility of highly reactive substrate peptides. Amino Acids. doi:10.1007/s00726-011-1131-8
Yamada K, Urisu A, Kakami M, Koyama H, Tokuda R, Wada E, Kondo Y, Ando H, Morita Y, Torii S (2000) IgE-binding activity to enzyme-digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion. Allergy 55:565–569
Yoo H, Ahn ER, Kim SJ, Lee SH, Oh SH, Kim SY (2012) Divergent results induced by different types of septic shock in transglutaminase 2 knockout mice. Amino Acids. doi:10.1007/s00726-012-1412-x
Zemskov EA, Janiak A, Hang J, Waghray A, Belkin AM (2006) The role of tissue transglutaminase in cell–matrix interactions. Front Biosci 11:1057–1076
Acknowledgments
The guest editors express their gratitude to Prof. Gert Lubec, Editor-in-Chief, for the opportunity to prepare this special issue of Amino Acids and all Authors for their commitment and contributions to this compilation and we trust that this will be the start of an expanding and long-standing partnership of Amino Acids with TGs research.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Beninati, S., Facchiano, F. & Piacentini, M. Transglutaminases: future perspectives. Amino Acids 44, 1–9 (2013). https://doi.org/10.1007/s00726-012-1431-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-012-1431-7