%0 Journal Article
%T Total 4EBP1 Is Elevated in Liver of Rats in Response to Low Sulfur Amino Acid Intake
%A Angelos K. Sikalidis
%A Kevin M. Mazor
%A Minji Kang
%A Hongyun Liu
%A Martha H. Stipanuk
%J Journal of Amino Acids
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/864757
%X Translation initiation is known to be regulated by the binding of eukaryotic initiation factor 4E (eIF4E) by binding proteins (4EBPs), and there is evidence that amino acid deprivation and other cellular stresses upregulate 4EBP1 expression. To pursue the question of whether diets limited in an essential amino acid lead to induction of 4EBP1 expression in vivo, diets that varied in methionine and cystine content were fed to rats for 7 days, and 4EBP1 mRNA and protein levels and 4EBP1 phosphorylation state were determined. Total 4EBP1 mRNA and protein abundance increased in liver of rats with severely deficient intakes of sulfur amino acids (0.23% or 0.11% methionine without cystine) but not in animals with a less restricted intake of sulfur amino acids (0.11% methionine plus 0.35% cystine) but a similarly restricted intake of total diet (53 to 62% of control). The amount of 4EBP1 binding activity (¦Á + ¦Â forms) was elevated in liver of rats fed sulfur amino acid-deficient diets, whereas the hyperphosphorylation of 4EBP1 was not affected by dietary treatment. Results suggest that changes in total 4EBP1 expression should be considered when examining mechanisms that attenuate protein synthesis during amino acid deficiency states. 1. Introduction Regulation of protein synthesis in eukaryotic cells occurs primarily at the initiation step of mRNA translation, during which ribosomal subunits are recruited to the mRNA through the action of eukaryotic initiation factors (eIFs). The regulation of mRNA translation initiation plays critical roles in the regulation of cell division, differentiation, growth, survival, and apoptosis, and dysregulation of translation initiation is associated with cancer, obesity, insulin resistance, and impaired responses to various stress situations [1¨C7]. The two best understood mechanisms for regulation of mRNA translation initiation are the regulation of formation of the ternary complex, which consists of the methionine-charged initiator tRNA, eIF2, and GTP, and the regulation of assembly of the eIF4F complex, which involves the association of the mRNA 5¡ä cap-binding protein eIF4E with eIF4G and eIF4A. Phosphorylation of the alpha subunit of eIF2 (eIF2¦Á) blocks ternary complex formation, thereby blocking formation of the 43S preinitiation complex and suppressing global translation. Mammals have four eIF2¦Á kinases that are activated by different types of cellular stress, including the unfolded protein response and amino acid deprivation, such that downstream effects of eIF2¦Á phosphorylation are shared among different stress-response
%U http://www.hindawi.com/journals/jaa/2013/864757/