TY - JOUR
T1 - Transglutaminase 5 is regulated by guanine-adenine nucleotides
AU - Candi, Eleonora
AU - Paradisi, Andrea
AU - Terrinoni, Alessandro
AU - Pietroni, Valentina
AU - Oddi, Sergio
AU - Cadot, Bruno
AU - Jogini, Vishwanath
AU - Meiyappan, Muthuraman
AU - Clardy, Jon
AU - Finazzi-Agro, Alessandro
AU - Melino, Gerry
PY - 2004/7/1
Y1 - 2004/7/1
N2 - Transglutaminases (TGases) are Ca2+-dependent enzymes capable of catalysing transamidation of glutamine residues to form intermolecular isopeptide bonds. Nine distinct TGases have been described in mammals, and two of them (types 2 and 3) are regulated by GTP/ATP. TGase2 hydrolyses GTP and is therefore a bifunctional enzyme. In the present study, we report that TGase5 is also regulated by nucleotides. We have identified the putative TGase5 GTP-binding pocket by comparative amino acid sequence alignment and homology-derived three-dimensional modelling. GTP and ATP inhibit TGase5 cross-linking activity in vitro, and Ca2+ is capable of completely reversing this inhibition. In addition, TGase5 mRNA is not restricted to epidermal tissue, but is also present in different adult and foetal tissues, suggesting a role for TGase5 outside the epidermis. These results reveal the reciprocal actions of Ca2+ and nucleotides with respect to TGase5 activity. Taken together, these results indicate that TGases are a complex family of enzymes regulated by calcium, with at least three of them, namely TGase2, TGase3 and TGase5, also being regulated by ATP and GTP.
AB - Transglutaminases (TGases) are Ca2+-dependent enzymes capable of catalysing transamidation of glutamine residues to form intermolecular isopeptide bonds. Nine distinct TGases have been described in mammals, and two of them (types 2 and 3) are regulated by GTP/ATP. TGase2 hydrolyses GTP and is therefore a bifunctional enzyme. In the present study, we report that TGase5 is also regulated by nucleotides. We have identified the putative TGase5 GTP-binding pocket by comparative amino acid sequence alignment and homology-derived three-dimensional modelling. GTP and ATP inhibit TGase5 cross-linking activity in vitro, and Ca2+ is capable of completely reversing this inhibition. In addition, TGase5 mRNA is not restricted to epidermal tissue, but is also present in different adult and foetal tissues, suggesting a role for TGase5 outside the epidermis. These results reveal the reciprocal actions of Ca2+ and nucleotides with respect to TGase5 activity. Taken together, these results indicate that TGases are a complex family of enzymes regulated by calcium, with at least three of them, namely TGase2, TGase3 and TGase5, also being regulated by ATP and GTP.
KW - Apoptosis
KW - GTP
KW - GTPase activity
KW - Transglutaminase
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U2 - 10.1042/BJ20031474
DO - 10.1042/BJ20031474
M3 - Article
C2 - 15038793
AN - SCOPUS:3142658637
VL - 381
SP - 313
EP - 319
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 1
ER -