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抗酶的强制表达消除鸟氨酸脱羧酶活性,抑制多胺的细胞水平并抑制细胞生长。

Forced expression of antizyme abolishes ornithine decarboxylase activity, suppresses cellular levels of polyamines and inhibits cell growth.

作者信息

Murakami Y, Matsufuji S, Miyazaki Y, Hayashi S

机构信息

Department of Nutrition, Jikei University School of Medicine, Tokyo, Japan.

出版信息

Biochem J. 1994 Nov 15;304 ( Pt 1)(Pt 1):183-7. doi: 10.1042/bj3040183.

Abstract

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.

摘要

鸟氨酸脱羧酶(ODC)是多胺生物合成中的关键酶。它是一种寿命较短的蛋白质,受其产物多胺的负调控。多胺诱导产生的ODC抑制蛋白——抗酶的结合可加速其降解。为评估抗酶的生理重要性,我们检测了抗酶的强制表达对细胞ODC、多胺水平及细胞生长的影响。抗酶几乎完全消除了生长刺激对ODC的诱导作用。这可能是由于抗酶诱导新合成的ODC快速降解所致,因为ODC与抗酶复合物的半衰期小于5分钟。抗酶的强制表达导致细胞内腐胺和亚精胺水平降低,并抑制细胞生长,添加腐胺可部分恢复细胞生长。这些观察结果表明抗酶在多胺代谢中起至关重要的作用。

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