Further Evidence against Post-transcriptional Control of Inducible Tyrosine Aminotransferase Synthesis in Cultured Hepatoma Cells

Abstract

THE paradoxical increase in concentration of specific proteins following treatment with inhibitors of macromolecular synthesis, a phenomenon sometimes termed ‘superinduction’, is rather frequently observed in eukaryotic cells. Tomkins et al.¹ listed some eighty reported observations of this kind that have been made in bacterial, plant, and animal systems and, while acknowledging that the mechanism involved has been analysed in only a few of these, argued that the frequency of effects of this kind in mammalian cells suggests that control of gene expression by post-transcriptional mechanisms is quite common. This suggestion stems from their analyses of the effects of actinomycin D on the inducible tyrosine amino- transferase in cultured hepatoma cells. These analyses have led to elaboration of a model involving a labile cytoplasmic repressor, which reversibly inhibits the translation of amino-transferase mRNA (ref. 2) and/or promotes mRNA degradation³. In this view, steroid-mediated induction can be attributed to inhibition by the hormone of either the synthesis or the activity of repressor. If correct, this model quite properly focuses attention on post-transcriptional control mechanisms as of primary interest in steroid-mediated enzyme induction and, by extension, in other mammalian regulatory systems as well.