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 biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importa...

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Bibliographic Details
Published in:Biochemical journal 1994-11, Vol.304 ( Pt 1) (1), p.183-187
Main Authors: Murakami, Y, Matsufuji, S, Miyazaki, Y, Hayashi, S
Format: Article
Language:English
Subjects:
Animals
Cell Division - drug effects
Cell Line
CHO Cells
Cricetinae
Dexamethasone - pharmacology
Ornithine Decarboxylase Inhibitors
Polyamines - metabolism
Proteins - metabolism
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Summary:Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importance of antizyme we examined the effect of forced expression of antizyme on cellular ODC and polyamine levels and cell growth. Antizyme almost completely abolished the induction of ODC by growth stimuli. This may have been caused by antizyme-induced rapid degradation of newly synthesized ODC, since the half-life of ODC complexes with antizyme was less than 5 min. Forced expression of antizyme caused reductions of cellular putrescine and spermidine levels, and inhibited cell growth, which was partially restored by the addition of putrescine. These observations suggested a critically important role of antizyme in polyamine metabolism.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3040183