FORCED EXPRESSION OF ANTIZYME ABOLISHES ORNITHINE DECARBOXYLASE ACTIVITY, SUPPRESSES CELLULAR-LEVELS OF POLYAMINES AND INHIBITS CELL-GROWTH

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesi s. It is a short-lived protein and negatively regulated by its product s, polyamines. Its degradation is accelerated by the binding of antizy me, an ODC-inhibitory protein induced by polyamines. To evaluate the p hysiological importance of antizyme we examined the effect of forced e xpression of antizyme on cellular ODC and polyamine levels and cell gr owth. Antizyme almost completely abolished the induction of ODC by gro wth stimuli. This may have been caused by antizyme-induced rapid degra dation of newly synthesized ODC, since the half-life of ODC complexed with antizyme was less than 5 min. Forced expression of antizyme cause d reductions of cellular putrescine and spermidine levels, and inhibit ed cell growth, which was partially restored by the addition of putres cine. These observations suggested a critically important role of anti zyme in polyamine metabolism.