The importance of the GTP‐binding protein tissue transglutaminase in the regulation of cell cycle progression

Abstract

Tissue transglutaminase (tTgase) is a GTP‐binding Ca²⁺‐dependent enzyme which catalyses the post‐translational modification of proteins via ϵ(γ‐glutamyl) lysine bridges. Recent evidence suggests that the GTP‐binding activity of tTgase may be important in intracellular signalling 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the full length tTgase cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine (Cys 277) has been replaced by serine.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.