Synthesis of the translational apparatus is regulated at the translationallevel

The synthesis of many mammalian proteins associated with the translational apparatus is selectively regulated by mitogenic and nutritional stimuli, at the translational level. The apparent advantages of the regulation of gene expression at the translational level are the speed and the readily revers ible nature of the response to altering physiological conditions. These two features enable cells to rapidly repress the biosynthesis of the translati onal machinery upon shortage of amino acids or growth arrest, thus rapidly blocking unnecessary energy wastage. Likewise, when amino acids are repleni shed or mitogenic stimulation is applied, then cells can rapidly respond in resuming the costly biosynthesis of the translational apparatus. A structu ral hallmark, common to mRNAs encoding many components of the translational machinery, is the presence of a 5' terminal oligopyrimidine tract (5'TOP), referred to as TOP mRNAs. This structural motif comprises the core of the translational cis-regulatory element of these mRNAs. The present review foc uses on the mechanism underlying the translational control of TOP mRNAs upo n growth and nutritional stimuli. A special emphasis is put on the pivotal role played by ribosomal protein S6 kinase (S6K) in this mode of regulation , and the upstream regulatory pathways, which might be engaged in transduci ng external signals into activation of S6K. Finally, the possible involveme nt of pyrimidine-binding proteins in the translational control of TOP mRNAs is discussed.