Fonzi W A
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92717.
J Biol Chem. 1989 Oct 25;264(30):18110-8.
The mechanism of yeast ornithine decarboxylase (ODC) regulation in response to polyamines was examined. ODC catalyzes the first step of polyamine biosynthesis, the conversion of ornithine to putrescine. ODC activity was modulated approximately 200-fold by varying the availability of polyamines. Variations in ODC activity were associated with parallel changes in the amount of active enzyme molecules. Regulation of ODC activity did not appear to be mediated by changes in the stability of the enzyme. The half-life of ODC was approximately 75 min and was unaffected by the availability of polyamines. Polyamines had no demonstrable effect on the transcriptional or translational stages of ODC expression. The amount of ODC mRNA and the number of ribosomes associated with the mRNA were constant despite the variations in ODC activity. Unlike translationally controlled genes, the regulation of ODC expression did not require either the 5'- or the 3'-untranslated regions of the ODC gene transcript. While gene dosage experiments indicated that negative trans-acting factors are involved in control of ODC expression, these implied factors did not appear to affect translation of ODC mRNA. The results are interpreted to suggest that polyamines regulate ODC expression at a post-translational step prior to assembly of the active form of the enzyme.
研究了酵母鸟氨酸脱羧酶(ODC)响应多胺的调控机制。ODC催化多胺生物合成的第一步,即鸟氨酸转化为腐胺。通过改变多胺的可利用性,ODC活性可被调节约200倍。ODC活性的变化与活性酶分子数量的平行变化相关。ODC活性的调节似乎不是由酶稳定性的变化介导的。ODC的半衰期约为75分钟,不受多胺可利用性的影响。多胺对ODC表达的转录或翻译阶段没有明显影响。尽管ODC活性有所变化,但ODC mRNA的量以及与该mRNA相关的核糖体数量是恒定的。与翻译控制基因不同,ODC表达的调控不需要ODC基因转录本的5'或3'非翻译区。虽然基因剂量实验表明负性反式作用因子参与了ODC表达的控制,但这些潜在因子似乎并未影响ODC mRNA的翻译。这些结果表明,多胺在酶活性形式组装之前的翻译后步骤调节ODC表达。