Feedback repression of ornithine decarboxylase synthesis mediated by antizyme.
Feedback repression of ornithine decarboxylase synthesis mediated by antizyme.
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抗酶介导的鸟氨酸脱羧酶合成的反馈抑制。
DOI：
10.1042/bj3200755
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Judd,GG
中科院分区：
文献类型：
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作者：
Mitchell,JL;Choe,CY;Judd,GG
亚精胺诱导抗酶以及由此导致的鸟氨酸脱羧酶 (ODC) 降解的增强已得到充分研究；然而，人们对亚精胺水平升高减少多胺生物合成酶合成的机制知之甚少。为了评估合成抑制的相对贡献，与 ODC 的增强降解不同，在过量产生稳定形式 ODC 的变异细胞系中操纵亚精胺水平。亚精胺不会选择性抑制这些变异细胞中的 ODC 合成，这支持了亚精胺减少正常细胞中 ODC 合成的概念，因为在抗酶水平升高的情况下，蛋白质的降解增强。通过使用兔网织红细胞裂解物对该模型进行了进一步的体外研究，该裂解物同时催化 ODC mRNA 翻译和抗酶刺激的 ODC 蛋白降解。抗酶强烈抑制标记氨基酸掺入正常大鼠 ODC 中。出乎意料的是，它还减少了编码酶形式的 ODC mRNA 种类的表观翻译，而这些酶形式不会因翻译后添加抗酶而不稳定。在麦芽提取物中未观察到抗酶对 ODC 翻译的影响，其中不存在抗酶诱导的降解。此外，删除 ODC 不稳定所必需的一小段抗酶（氨基酸残基 113-118）会产生结合 ODC 但不会减弱其表观翻译的形式。这些结果表明，抗酶与ODC的共翻译添加产生的复合物不同于翻译后添加抗酶时形成的复合物，并且本质上不太稳定。
The induction of antizyme by spermidine and the resulting enhancement of ornithine decarboxylase (ODC) degradation have been well studied; however, little is known about the mechanism whereby elevated spermidine levels decrease synthesis of the polyamine biosynthetic enzyme. To evaluate the relative contribution of inhibited synthesis, as distinct from enhanced degradation of ODC, spermidine levels were manipulated in a variant cell line that overproduces a stable form of ODC. Spermidine did not selectively inhibit ODC synthesis in these variant cells, supporting the concept that spermidine diminishes ODC synthesis in normal cells owing to enhanced degradation of the protein in the presence of elevated antizyme levels. This model was further investigatedin vitroby use of rabbit reticulocyte lysate, which catalyses simultaneous ODC mRNA translation and antizyme-stimulated degradation of ODC protein. Antizyme strongly repressed the incorporation of labelled amino acids into normal rat ODC. Unexpectedly it also diminished the apparent translation of ODC mRNA species coding for enzyme forms that are not destabilized by the post-translational addition of antizyme. The effect of antizyme on ODC translation was not observed in wheatgerm extract, in which there is no antizyme-induced degradation. Further, deletion of a short segment of antizyme necessary for the destabilization of ODC (amino acid residues 113–118) resulted in a form that bound ODC but did not diminish its apparent translation. These results suggest that the co-translational addition of antizyme to ODC results in a complex that is different from, and innately less stable than, that formed when antizyme is added post-translationally.