Differential post-transcriptional control of ornithine decarboxylase and spermidine-spermine N1-acetyltransferase by polyamines

Abstract

Ornithine decarboxylase (ODC) and spermidine/spermine N 1-acetyltransferase (SSAT) are short-lived polyamine enzymes with rate-limiting roles in controlling polyamine biosynthesis and catabolism, respectively. We have found that treatment of MALME-3M human melanoma cells for 6 h with 10 μg/ml cycloheximide (CHX) increases ODC and SSAT mRNA 6–9-fold. When cells containing CHX-induced SSAT mRNA were washed and post-incubated for an additional 6 h in drug free media, enzyme activity increased only 2-fold above that in untreated cells despite the > 6-fold increase in accumulated mRNA. Inclusion of 10 μM spermine or spermidine in the post-incubation medium increased SSAT activity ∼7-fold without further elevating SSAT mRNA levels. This indicates post-transcriptional regulation which, due to the similarity between polyamine-mediated increases in SSAT activity and available mRNA, probably occurs at the level of mRNA translation. In contrast to the SSAT response, polyamines markedly reduced ODC activity (but not mRNA) to one sixth that in cells not exposed to polyamines. The findings illustrate how via post-transcriptional mechanisms, shifts in intracellular polyamine pools can simultaneously and differentially regulate polyamine biosynthesis and catabolism. It is hypothesized that these post-transcriptional responses enable cells to rapidly and sensitively control intracellular spermidine and spermine pools.