Beninati S, Gentile V, Caraglia M, Lentini A, Tagliaferri P, Abbruzzese A
Department of Biology, II University of Rome, Tor Vergata, Italy.
FEBS Lett. 1998 Oct 16;437(1-2):34-8. doi: 10.1016/s0014-5793(98)01191-0.
Post-translational formation of hypusine in eukaryotic initiation factor 5A (eIF-5A) is essential for cell viability. Recently, we showed that hypusine protein is an in vitro substrate for transglutaminases (TGases). 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% increase of gamma-glutamyl-omega-hypusine formation. Such changes were paralleled by a consistent decrease in the free polyamine pool and an enhancement of their excretion and of the formation of their gamma-glutamyl derivatives. These effects occurred together with a significant reduction of cell proliferation. In this report we suggest, for the first time, that tTGase affects hypusine metabolism, thus regulating the eIF-5A activity and cell proliferation.
真核生物起始因子5A(eIF-5A)中hypusine的翻译后形成对细胞活力至关重要。最近,我们发现hypusine蛋白是转谷氨酰胺酶(TGases)的体外底物。我们报告了组织TGase表达对体内hypusine代谢途径的影响。tTGase在BALB/c 3T3细胞中的稳定表达导致hypusine水平降低100倍,γ-谷氨酰-ω-hypusine形成增加50%。这些变化伴随着游离多胺池的持续减少以及它们的排泄和γ-谷氨酰衍生物形成的增加。这些效应同时伴随着细胞增殖的显著减少。在本报告中,我们首次提出tTGase影响hypusine代谢,从而调节eIF-5A活性和细胞增殖。