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Reciprocal Regulation of Ornithine Decarboxylase Degradation by Antizyme and Antizyme Inhibitor.

抗酶和抗酶抑制剂对鸟氨酸脱羧酶降解的相互调节。

基本信息

批准号：
06680625
负责人：
HAYASHI Shin-ichi
金额：
$ 1.41万
依托单位：
The Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680625/
关键词：
Ornithine decarboxylase Antizyme Antizyme inhibitor Polyamines cDNA Xenopus Tetrahymena Frameshifting cDNA タンパク質分解

项目摘要

Cellular level of ornithine decarboxylase (ODC) is under negative feedback regulation by its products putrescine and polyamines. We elucidated previously that polyamine-induced regulatory protein, antizyme (AZ), binds with ODC,destabilizing it. We also found another possible regulatory protein, antizyme inhibitor (AI), which is of similar size with ODC and binds with AZ with higher affinity than ODC.Following results were obtained by the present study.1. Sequence analysis of AI cDNA cloned from rat heart cDNA library revealed that AI is a protein consisting of 448 amino acids, which is highly homologous (47.5 percent identity) to, but clearly distinct from rat ODC,lacking PEST containing C-terminal region essential for rapid degradation. This result excluded the possibility that AI is some post-translational derivative of ODC.2. Examination of the effect of forced expression of transfected AI is under way right now with no firm result yet.3. AZ cDNA was isolated from the liver of Xenopus laevis and its sequence determined. The frog AZ cDNA had 63 percent homology with rat AZ cDNA and had a similar structure with rat cDNA that necessitates polyamine-induced ribosomal frameshifting for its translation. Although polysmines caused mild suppression of ODC in a protozoa Tetrahymena, the rate of ODC degradation was not affected by polyamines and ODC inhibitory factor, of either free or complexed form, was not detected in the cell extract, suggesting that repression of ODC synthesis alone is responsible for the polyamine-caused suppression of ODC in the protozoan cells.

鸟氨酸脱羧酶（ODC）的细胞水平受到其产物腐胺和多胺的负反馈调节。我们之前阐明了多胺诱导的调节蛋白抗酶 (AZ) 与 ODC 结合，使其不稳定。我们还发现了另一种可能的调节蛋白——抗酶抑制剂(AI)，它与ODC大小相似，与AZ的结合亲和力比ODC更高。本研究得到以下结果： 1．对从大鼠心脏cDNA文库中克隆的AI cDNA进行序列分析表明，AI是一种由448个氨基酸组成的蛋白质，与大鼠ODC高度同源（47.5％同一性），但与大鼠ODC明显不同，缺乏含有快速降解所必需的C端区域的PEST。这一结果排除了 AI 是 ODC.2 的某种翻译后衍生物的可能性。目前正在研究转染AI强制表达的效果，尚未有确切结果。3．从非洲爪蟾的肝脏中分离出 AZ cDNA，并测定了其序列。青蛙 AZ cDNA 与大鼠 AZ cDNA 具有 63% 的同源性，并且与大鼠 cDNA 具有相似的结构，因此其翻译需要多胺诱导的核糖体移码。尽管多胺对原生动物四膜虫中的 ODC 产生轻度抑制，但 ODC 降解速率不受多胺的影响，并且在细胞提取物中未检测到游离或复合形式的 ODC 抑制因子，这表明单独抑制 ODC 合成是多胺引起的原生动物细胞中 ODC 抑制的原因。