DIFFERENTIAL POSTTRANSCRIPTIONAL CONTROL OF ORNITHINE DECARBOXYLASE AND SPERMIDINE-SPERMINE N-1-ACETYLTRANSFERASE BY POLYAMINES

Ornithine decarboxylase (ODC) and spermidine/spermine N-1-acetyltransf erase (SSAT) are short-lived polyamine enzymes with rate-limiting role s in controlling polyamine biosynthesis and catabolism, respectively, We have found that treatment of MALME-3M human melanoma cells for 6 h with 10 mu g/ml cycloheximide (CHX) increases ODC and SSAT mRNA 6-9-fo ld, When cells containing CHX-induced SSAT mRNA were washed and post-i ncubated for an additional 6 h in drug free media, enzyme activity inc reased only 2-fold above that in untreated cells despite the >6-fold i ncrease in accumulated mRNA, Inclusion of 10 mu M spermine or spermidi ne in the post-incubation medium increased SSAT activity similar to 7- fold without further elevating SSAT mRNA levels, This indicates post-t ranscriptional regulation which, due to the similarity between polyami ne-mediated increases in SSAT activity and available mRNA, probably oc curs at the level of mRNA translation, In contrast to the SSAT respons e, polyamines markedly reduced ODC activity (but not mRNA) to one sixt h that in cells not exposed to polyamines. The findings illustrate how via post-transcriptional mechanisms, shifts in intracellular polyamin e pools can simultaneously and differentially regulate polyamine biosy nthesis and catabolism. It is hypothesized that these post-transcripti onal responses enable cells to rapidly and sensitively control intrace llular spermidine and spermine pools.