The importance of the GTP-binding protein tissue transglutaminase in the regulation of cell cycle progression.
Tissue transglutaminase (tTgase) is a GTP-binding Ca(2+)-dependent enzyme which catalyses the post-translational modification of proteins via epsilon(gamma-glutamyl) lysine bridges. Recent evidence suggests that the GTP-binding activity of tTgase may be important in intracellular signaling thus explaining some of the diverse suggested roles for the enzyme. In the following work a malignant hamster fibrosarcoma (Met B) has been stably transfected with both the full length tTgase cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine (Cys 277) has been replaced by serine. Expression of this mutant cDNA leads to a protein with GTP binding activity which is deficient of protein crosslinking activity. When synchronised into S-phase and allowed to progress through the cell cycle tTgase transfected clones (both mutant and wild type), when compared to transfected controls, show a delayed progression from S-phase to G2/M when analysed by flow cytometry which appears to be elicited by the G-protein activity of the tTgase.
Mian
S
S
Department of Life Sciences, Nottingham Trent University, UK.
el Alaoui
S
S
Lawry
J
J
Gentile
V
V
Davies
P J
PJ
Griffin
M
M
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D006224:Cricetinae; D003545:Cysteine; D004247:DNA / Q000096:biosynthesis; D005354:Fibrosarcoma; D019204:GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D012694:Serine; D014162:Transfection; D011503:Transglutaminases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D012694:Serine; D004247:DNA; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003545:Cysteine