TISSUE TRANSGLUTAMINASE EXPRESSION AFFECTS HYPUSINE METABOLISM IN BALB C 3T3 CELLS/

Post-translational formation of hypusine in eukaryotic initiation fact or 5A (eIF-5A) is essential for cell viability. Recently, we showed th at hypusine protein is an in vitro substrate for transglutaminases (TG ases), We report the effect of tissue TGase expression on the in vivo hypusine metabolic pathway. The stable expression of tTGase in BALB/c 3T3 cells induced a 100-fold reduction of hypusine levels and a 50% in crease of gamma-glutamyl- <(omega)over bar>-hypusine formation. Such c hanges mere paralleled by a consistent decrease in the free polyamine pool and an enhancement of their excretion and of the formation of the ir gamma- glutamyl derivatives, These effects occurred together with a significant reduction of cell proliferation, in this report we sugges t, for the first time, that tTGase affects hypusine metabolism, thus r egulating the eIF-5A activity and cell proliferation. (C) 1998 Federat ion of European Biochemical Societies.