Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression.

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Nilsson J, Grahn B, Heby O

Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression.

Biochem J. 2000 Mar 15;346 Pt 3:699-704.

PubMed ID

10698696 [ View in PubMed

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Abstract

Ornithine decarboxylase (ODC) catalyses the first step in the synthesis of the polyamines putrescine, spermidine and spermine. The polyamines are essential for cell growth, but at elevated levels they may be tumorigenic, toxic, or may induce apoptosis. Therefore, ODC activity is highly regulated. It is induced when cells are stimulated to grow, and it is subjected to feedback inhibition by the polyamines. By causing ribosomal frameshifting, polyamines induce the synthesis of antizyme, a 23-kDa protein, which binds to ODC, inhibits its activity and promotes its degradation by the 26 S proteasome. Antizyme, in turn, is inhibited by antizyme inhibitor (AZI). We describe the cloning of a mouse AZI cDNA, encoding a protein with high homology to mouse ODC. Using purified recombinant proteins, we show that AZI (which has no ODC activity) can release enzymically active ODC from antizyme suppression in vitro. We also show that ODC reactivation takes place in mouse fibroblasts upon transient transfection with an AZI-expressing plasmid construct. Finally we demonstrate that the AZI mRNA content of mouse fibroblasts increases significantly within an hour of growth stimulation, i.e. much earlier than ODC transcripts. Our results indicate that induction of AZI synthesis may represent a means of rescuing ODC molecules that have been inactivated and tagged for degradation by antizyme, when culture conditions improve and polyamine production is needed for cell growth and proliferation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Spermine	Ornithine decarboxylase	Protein	Humans	Unknown	Product of	Details