Antizyme2 is a negative regulator of ornithine decarboxylase and polyaminetransport

The antizyme family consists of closely homologous proteins believed to reg ulate cellular polyamine pools. Antizyme1, the first described, negatively regulates ornithine decarboxylase, the initial enzyme in the biosynthetic p athway for polyamines, Antizyme1 targets ornithine decarboxylase for degrad ation and inhibits polyamine transport into cells, thereby diminishing poly amine pools. A polyamine-stimulated ribosomal frameshift is required for de coding antizyme1 mRNA. Recently, additional novel conserved members of the antizyme family have been described. We report here the properties of one o f these, antizyme2. Antizyme2, like antizyme1, binds to ornithine decarboxy lase and inhibits polyamine transport. Using a baculovirus expression syste m in cultured Sf21 insect cells, both antizymes were found to accelerate or nithine decarboxylase degradation. Expression of either antizyme1 or 2 in S f21 cells also diminished their uptake of the polyamine spermidine. Both fo rms of antizyme can therefore function as negative regulators of polyamine production and transport. However, in contrast to antizyme1, antizyme2 has negligible ability to stimulate degradation of ornithine decarboxylase in a rabbit reticulocyte lysate.