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https://hdl.handle.net/2440/82362
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Type: | Journal article |
Title: | A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B |
Author: | Wang, X. Proud, C. |
Citation: | Molecular and Cellular Biology, 2008; 28(5):1429-1442 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2008 |
ISSN: | 0270-7306 1098-5549 |
Statement of Responsibility: | Xuemin Wang and Christopher G. Proud |
Abstract: | Eukaryotic initiation factor 2B (eIF2B) plays a key role in controlling the initiation of mRNA translation. eIF2B is heteropentamer whose catalytic (ε) subunit promotes GDP/GTP exchange on eIF2. We show here that depriving human cells of amino acids rapidly results in the inhibition of eIF2B, independently of changes in eIF2 phosphorylation. Although amino acid deprivation also inhibits signaling through the mammalian target of rapamycin complex 1 (mTORC1), the inhibition of eIF2B activity by amino acid starvation is independent of mTORC1. Instead, amino acids repress the phosphorylation of a novel site in eIF2Bε. We identify this site as Ser525, located adjacent to the known phosphoregulatory region in eIF2Bε. Mutation of Ser525 to Ala abolishes the regulation of eIF2B and protein synthesis by amino acids. This indicates that phosphorylation of this site is crucial for the control of eIF2B and protein synthesis by amino acids. These findings identify a new way in which amino acids regulate a key step in translation initiation and indicate that this involves a novel amino acid-sensitive signaling mechanism. |
Keywords: | Kidney Cells, Cultured Cell Line Cell Line, Tumor Jurkat Cells Fibroblasts Animals Humans Mice Carcinoma, Hepatocellular Liver Neoplasms Cycloheximide Amino Acids Alanine Histidine Serine Eukaryotic Initiation Factor-2B Luciferases, Renilla Protein Synthesis Inhibitors Peptide Mapping Transfection Amino Acid Substitution Protein Biosynthesis Catalytic Domain Protein Structure, Tertiary Phosphorylation Genes, Reporter Models, Biological Time Factors Embryo, Mammalian |
Rights: | Copyright © 2008, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/MCB.01512-07 |
Published version: | http://dx.doi.org/10.1128/mcb.01512-07 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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