Antizyme2 Is a Negative Regulator of Ornithine Decarboxylase and Polyamine Transport*

Antizyme2 Is a Negative Regulator of Ornithine Decarboxylase and Polyamine Transport*
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DOI:
10.1074/jbc.274.37.26425
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发表时间:
1999-09
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
C. Zhu;D. Wayne Lang;P. Coffino
C. Zhu;D. Wayne Lang;P. Coffino
中科院分区:
其他
文献类型:
--
作者:
C. Zhu;D. Wayne Lang;P. Coffino

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抗酶家族由被认为调控细胞多胺池的同源蛋白组成。首先描述的Antizyme1负性调节鸟氨酸脱羧酶,鸟氨酸脱羧酶是多胺生物合成途径中的初始酶。Antizyme1靶向鸟氨酸脱羧酶降解并抑制多胺转运到细胞中,从而减少多胺池。解码抗酶1 mRNA需要多胺刺激的核糖体移码。最近,新的保守的抗酶家族成员已经被描述。我们在此报告其中一种,antizyme2的性质。与antizyme1一样,Antizyme2与鸟氨酸脱羧酶结合并抑制多胺运输。在培养的Sf21昆虫细胞中使用杆状病毒表达系统,发现这两种抗酶都能加速鸟氨酸脱羧酶的降解。抗酶1或抗酶2在Sf21细胞中的表达也减少了它们对多胺亚精胺的摄取。因此,这两种形式的抗酶都可以作为多胺产生和运输的负调节因子发挥作用。然而,与antizyme1相比,antizyme2在兔网织细胞裂解物中刺激鸟氨酸脱羧酶降解的能力可以忽略不计。
The antizyme family consists of closely homologous proteins believed to regulate cellular polyamine pools. Antizyme1, the first described, negatively regulates ornithine decarboxylase, the initial enzyme in the biosynthetic pathway for polyamines. Antizyme1 targets ornithine decarboxylase for degradation and inhibits polyamine transport into cells, thereby diminishing polyamine pools. A polyamine-stimulated ribosomal frameshift is required for decoding antizyme1 mRNA. Recently, additional novel conserved members of the antizyme family have been described. We report here the properties of one of these, antizyme2. Antizyme2, like antizyme1, binds to ornithine decarboxylase and inhibits polyamine transport. Using a baculovirus expression system in cultured Sf21 insect cells, both antizymes were found to accelerate ornithine decarboxylase degradation. Expression of either antizyme1 or 2 in Sf21 cells also diminished their uptake of the polyamine spermidine. Both forms 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.