Inactive and Highly Active, Proteolytically Processed Transglutaminase-5 in Epithelial Cells

Valentina Pietroni, Sabrina Di Giorgi, Andrea Paradisi, Bijan Ahvazi, Eleonora Candi and Gerry Melino


Journal of Investigative Dermatology (2008) 128, 2760–2766


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Transglutaminases (TGs) are Ca2þ-dependent enzymes capable of catalyzing transamidation of glutamine residues to form intermolecular isopeptide bonds. These enzymes are involved in various biological phenomena, including blood coagulation, wound healing, cell death, tissue repair, and terminal differentiation of keratinocytes. Among the TG-family members, TG5 is one of the latest identified enzymes and therefore the less characterized at the functional level. In this work, we reported that TG5 is proteolytically processed in the baculovirus expression system and in mammal epithelial cells. Similar to other members of the TG family—TG1, TG3, and factor XIIIa -, TG5 full-length enzyme has very low enzymatic activity, while the 53-kDa proteolytically
processed form is highly active.


Aeschlimann D, Koeller MK, Allen-Hoffmann BL, Mosher DF (1998) Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes. Detection and identification of transglutaminase gene products based on reverse transcription–polymerase chain reaction with degenerate primers. J Biol Chem 273:3452–60

Ahvazi B, Boeshans KM, Idler W, Baxa U, Steinert PM (2003) Roles of calcium ions in the activation and activity of the transglutaminase 3 enzyme. J Biol Chem 278:23834–41

Ahvazi B, Boeshans KM, Idler W, Baxa U, Steinert PM, Rastinejad F (2004a) Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium. J Biol Chem 279:7180–92

Ahvazi B, Boeshans KM, Rastinejad F (2004b) The emerging structural understanding of transglutaminase 3. J Struct Biol 147:200–7

Candi E, Oddi S, Paradisi A, Terrinoni A, Ranalli M, Teofoli P et al. (2002) Expression of transglutaminase 5 in normal and pathologic human epidermis. J Invest Dermatol 119:670–7

Candi E, Oddi S, Terrinoni A, Paradisi A, Ranalli M, Finazzi-Agro A et al. (2001) Transglutaminase 5 cross-links loricrin, involucrin, and small proline-rich proteins in vitro. J Biol Chem 276:35014–23

Candi E, Paradisi A, Terrinoni A, Pietroni V, Oddi S, Cadot B et al. (2004) Transglutaminase 5 is regulated by guanine–adenine nucleotides. Biochem J 381:313–9

Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6:328–40

Cassidy AJ, van Steensel MA, Steijlen PM, van Geel M, van der Velden J, Morley SM et al. (2005) A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet 77:909–17

Cheng T, Hitomi K, van Vlijmen-Willems IM, de Jongh GJ, Yamamoto K, Nishi K et al. (2006) Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumainbinding site. A novel clue for the role of cystatin M/E in epidermal cornification. J Biol Chem 281:15833–9

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 276:3295–301

Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA (2005) Transglutaminase function in epidermis. J Invest Dermatol 124:481–92

Esposito C, Caputo I (2005) Mammalian transglutaminases. Identification of substrates as a key to physiological and physiopathological relevance. FEBS J 272:615–31

Greenberg CS, Birckbichler PJ, Rice RH (1991) Transglutaminase: multifunctional cross-linking enzymes that stabilize tissues. FASEB J 5:3071–7

Griffin M, Casadio R, Bergamini CM (2002) Transglutaminases: nature’s biological glues. Biochem J 368:377–96

Hitomi K, Horio Y, Ikura K, Yamanishi K, Maki M (2001) Analysis of epidermal-type transglutaminase (TG 3) expression in mouse tissues and cell lines. Int J Biochem Cell Biol 33:491–8

Hitomi K, Kanehiro S, Ikura K, Maki M (1999) Characterization of mouse epidermal-type transglutaminase (TG 3): regulation of its activity by proteolysis and guanine nucleotides. J Biochem (Tokyo) 125:1048–54

Hitomi K, Yamagiwa Y, Ikura K, Yamanishi K, Maki M (2000) Characterization of human recombinant transglutaminase 1 purified from baculovirus-infected insect cells. Biosci Biotechnol Biochem 64:2128–37

Hohl D, Aeschlimann D, Huber M (1998) In vitro and rapid in situ transglutaminase assays for congenital ichthyoses—a comparative study. J Invest Dermatol 110:268–71

Kalinin AE, Kajava AV, Steinert PM (2002) Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays 24:789–800

Kim HC, Lewis MS, Gorman JJ, Park SC, Girard JE, Folk JE et al. (1990) Protransglutaminase E from guinea pig skin. J Biol Chem 265:21971–8

Kim SY, Chung SI, Steinert PM (1995) Highly active soluble processed forms of the transglutaminase 1 enzyme in epidermal keratinocytes. J Biol Chem 270:18026–35

Liu S, Cerione RA, Clardy J (2002) Structural basis for the guanine nucleotidebinding activity of tissue transglutaminase and its regulation of transamidation activity. Proc Natl Acad Sci USA 99:2743–7

Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–56

Muszbek L, A´ da´ny R, Mikkola H (1996) Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation and function. Crit Rev Lab Sci 33:357–421

Muszbek L, Yee VC, Hevessy Z (1999) Blood coagulation factor XIII: structure and function. Thromb Res 42:271–305

Shemirani AH, Haramura G, Bagoly Z, Muszbek L (2006) The combined effect of fibrin formation and factor XIII A subunit Val34Leu polymorphism on the activation of factor XIII in whole plasma. Biochim Biophys Acta 1764:1420–3

Steinert PM, Chung SI, Kim SY (1996a) Inactive zymogen and highly active proteolytically processed membrane-bound forms of the transglutaminase 1 enzyme in human epidermal keratinocyte. Biochem Biophys Res Commun 221:101–6

Thacher SM (1989) Purification of keratinocyte transglutaminase and its expression during squamous differentiation. J Invest Dermatol 92:578–84

Thacher SM, Rice RH (1985) Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell 40:685–95

Thibaut S, Candi E, Pietroni V, Melino G, Schmidt R, Bernard BA (2005) Transglutaminase 5 expression in human hair follicle. J Invest Dermatol 125:581–5

Zocchi L, Terrinoni A, Candi E, Ahvazi B, Bagetta G, Corasaniti MT et al. (2007) Identification of transglutaminase 3 splicing isoforms. J Invest Dermatol 127:1791–4

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