Regulation of ornithine decarboxylase during cell growth. Changes in the stability and translatability of the mRNA, and in the turnover of the protein.

Abstract

When Ehrlich ascites tumor cells were stimulated to grow, their ornithine decarboxylase (ODC) activity increased 20- to 30-fold. The increase in ODC mRNA content was one order of magnitude less during the corresponding period. Likewise, the subsequent changes in ODC activity failed to show proportionality to those of the ODC mRNA content. The changes in ODC activity were not attributable to changes in ODC turnover, even though the half-life of the enzyme decreased from 56 min during the period of increasing, to 36 min during the period of decreasing ODC activity. There was no evidence of an activation-inactivation-cycle for the enzyme. In view of these findings it appears that ODC mRNA alterations are amplified mainly at the translational level. The biphasic change in ODC mRNA content was partly attributable to a change in turnover of the message, as determined after inhibition of transcription with actinomycin D. Thus, the ODC mRNA half-life was estimated to decrease from 8.7 h during the period of increasing ODC activity to 4.0 h during the period of decreasing ODC activity. Despite the inhibition of transcription by actinomycin D, there was a marked superinduction of ODC activity. Our data demonstrate that the regulation of ODC expression is a complex phenomenon, involving controls at many levels.