Studies on the regulation of ornithine decarboxylase in yeast:: Effect of deletion in the MEU1 gene

被引:10
作者
Chattopadhyay, MK [1 ]
Tabor, CW [1 ]
Tabor, H [1 ]
机构
[1] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA
关键词
methylthioadenosine; methylthioadenosine phosphorylase; polyamines; spermidine; putrescine;
D O I
10.1073/pnas.0507299102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Methylthioadenosine is formed during the biosynthesis of spermidine and of spermine and is metabolized by methylthioadenosine phosphorylase, an enzyme missing in several tumor cell lines. In Saccharomyces cerevisiae, this enzyme is coded by the MEW gene. We have now studied the effect of the meu1 deletion on polyamine metabolism in yeast. We found that the effects of the meu1 Delta mutation mostly depend on the stage of cell growth. As the cell density increases, there is a marked fall in the level of ornithine decarboxylase (ODC) in the MEU1(+) cells, which we show is caused by an antizyme-requiring degradation system. In contrast, there is only a small decrease in the ODC level in the meu1 Delta cells. The meu1 Delta cells have a higher putrescine and a lower spermidine level than MEU1+ cells, suggesting that the decreased spermidine level in the meu1 Delta cultures is responsible for the greater apparent stability of ODC in the meu1 Delta cells. The lower spermidine level in the meu1 Delta cells probably results from an inhibition of spermidine synthase by the methylthioadenosine that presumably accumulates in these mutants. In both MEU1(+) and the meu1 Delta cultures, the ODC levels were markedly decreased by the addition of spermidine to the media, and thus our results contradict the postulation of Subhi et al. [Subhi, A. L., et al. (2003) J. Bio/. Chem. 278, 4986849873] of a novel regulatory pathway in meu1A cells in which ODC is not responsive to spermicline.
引用
收藏
页码:16158 / 16163
页数:6
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