Translational control during amino acid starvation.

Amino acid starvation of mammalian cells results in a pronounced fall in the overall rate of protein synthesis. This is associated with increased phosphorylation of the alpha-subunit of the initiation factor eIF-2, which in turn impairs the activity of the guanine nucleotide exchange factor, eIF-2B. Similar mechanisms have now been found to operate in the yeast, Saccharomyces cerevisiae, where the major physiological result is to circumvent the lack of external amino acids by promoting the translation of a transcription factor, GCN4, that facilitates the expression of a number of enzymes required for amino acid biosynthesis. This article reviews current knowledge of these mechanisms in both mammalian and yeast cells and identifies questions still requiring elucidation.