GROWTH-CONTROL OF TRANSLATION IN MAMMALIAN-CELLS

Most cells in a mammalian organism are not proliferating, but are in a quiescent, resting state referred to as “G0.” This chapter discusses the growth control of translation in mammalian cells. Production of many early-response proteins is regulated by the level of their respective messenger RNA (mRNA) molecules. Although mRNA levels are involved in a major way in growth control, there are also a number of older observations in the literature that argue compellingly for a substantial role for the regulation of preformed mRNA molecules translation. The level and/or activity of translational initiation factors can influence the rates of both protein synthesis and cell proliferation. The translation of mRNA molecules can be regulated through the specific binding of translational repressor proteins. The classical example is the regulation of expression of the intracellular iron-binding protein, ferritin, by the availability of iron. The regulation of the translation of a preformed mRNA in response to a stimulus enables a cell to alter the rate of synthesis of a protein product considerably more rapidly than would be possible by a change in transcription rate. Many of the genes that show an element of translational control encode products with profound physiological influences such as proto-oncogenes. The possibility of translational regulation of these mRNAs provides for secure repression of their expression at inappropriate times and for fine-tuning their expression at proper times in the cell cycle and during development. Many cellular studies strongly suggest that a significant fraction of the new protein synthesis after mitogenic stimulation is due to the activation of the translation of pre-existing mRNA molecules. © 1995, Academic Press Inc.