Studies on the regulation of ornithine decarboxylase in yeast: effect of deletion in the MEU1 gene.
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 MEU1 gene. We have now studied the effect of the meu1 deletion on polyamine metabolism in yeast. We found that the effects of the meu1Delta 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 meu1Delta cells. The meu1Delta cells have a higher putrescine and a lower spermidine level than MEU1(+) cells, suggesting that the decreased spermidine level in the meu1Delta cultures is responsible for the greater apparent stability of ODC in the meu1Delta cells. The lower spermidine level in the meu1Delta cells probably results from an inhibition of spermidine synthase by the methylthioadenosine that presumably accumulates in these mutants. In both MEU1(+) and the meu1Delta 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. Biol. Chem. 278, 49868-49873] of a novel regulatory pathway in meu1Delta cells in which ODC is not responsive to spermidine.
Chattopadhyay
Manas K
MK
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 223, Bethesda, MD 20892, USA.
Tabor
Celia White
CW
Tabor
Herbert
H
D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000254:growth & development; D013095:Spermidine / Q000032:analysis / Q000494:pharmacology
C014632:2-keto-4-methylthiobutyric acid; D008715:Methionine; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009955:Ornithine Decarboxylase; D013095:Spermidine