Total 4E‐BP1 Levels are Elevated in Livers of Rats Fed Diets Low in Protein or Sulfur Amino Acids

Coping with nutrient deficiency is an essential survival advantage for organisms. Mammalian cells respond to amino acid limitation and suppress protein synthesis via the phosphorylation of eIF2alpha or via suppression of the mTOR pathway by reducing the phosphorylation of 4E‐BP1 and rpS6. Here we propose the possibility of a third mechanism for translation suppression when amino acids are deficient, the induction of protein levels of total 4E‐BP1. Rats were fed various protein‐ or amino acid‐deficient diets that resulted in different degrees of growth inhibition. In these experiments we consistently observed a significant induction of total 4E‐BP1 protein levels in liver of rats fed diets deficient in protein or sulfur amino acids that did not parallel a reduction in 4E‐BP1 phosphorylation and that was independent of energy restriction or reduced feed intake. Furthermore, the induction of total 4E‐BP1 appeared independent of eIF2alpha phosphorylation. Protein translation initiation may be inhibited by increased abundance of 4E‐BP1 in response to essential amino acid deprivation. Supported by NIDDKD Grant # DK083473.