Regulated degradation of yeast ornithine decarboxylase

Ornithine decarboxylase (ODC) declines in cells that accumulate an excess o f polyamines, the downstream products of the enzyme, Superfluous production of polyamines is thus prevented. In animal cells, polyamines reduce ODC ac tivity by accelerating its degradation. Similar down-regulation of ODC acti vity has been observed in the budding yeast Saccharomyces cerevisiae, but i nduced degradation has not been documented. Here we show using pulse-chase analysis that the loss of enzyme activity is the result of increased degrad ation of ODC. Polyamines reduce the half-life of the newly synthesized prot ein from 3 h to approximately 10 min. Degradation of bulk ODC pools is also accelerated by polyamines, but the absolute rate of turnover is slower, wi th a half-life of 5 h in untreated and 1 h in treated cells. Newly synthesi zed ODC polypeptide thus undergoes a process of maturation that renders it relatively resistant to both basal and polyamine-induced degradation. Prote asome mutants have a blunted or absent regulatory response, implicating bot h the core protease and the regulatory cap of the proteasome in induced deg radation of yeast ODC.