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Regulation of mammalian translation factors by nutrients

Proud, C.G. (2002) Regulation of mammalian translation factors by nutrients European Journal of Biochemistry, 269, (22), pp. 5338-5349. (doi:10.1046/j.1432-1033.2002.03292.x).

Record type: Article

Abstract

Protein synthesis requires both amino acids, as precursors, and a substantial amount of metabolic energy. It is well established that starvation or lack of nutrients impairs protein synthesis in mammalian cells and tissues. Branched chain amino acids are particularly effective in promoting protein synthesis. Recent work has revealed important new information about the mechanisms involved in these effects. A number of components of the translational machinery are regulated through signalling events that require the mammalian target of rapamycin, mTOR. These include translational repressor proteins (eukaryotic initiation factor 4E-binding proteins, 4E-BPs) and protein kinases that act upon the small ribosomal subunit (S6 kinases). Amino acids, especially leucine, positively regulate mTOR signalling thereby relieving inhibition of translation by 4E-BPs and activating the S6 kinases, which can also regulate translation elongation. However, the molecular mechanisms by which amino acids modulate mTOR signalling remain unclear. Protein synthesis requires a high proportion of the cell's metabolic energy, and recent work has revealed that metabolic energy, or fuels such as glucose, also regulate targets of the mTOR pathway. Amino acids and glucose modulate a further important regulatory step in translation initiation, the activity of the guanine nucleotide-exchange factor eIF2B. eIF2B controls the recruitment of the initiator methionyl-tRNA to the ribosome and is activated by insulin. However, in the absence of glucose or amino acids, insulin no longer activates eIF2B. Since control of eIF2B is independent of mTOR, these data indicate the operation of additional, and so far unknown, regulatory mechanisms that control eIF2B activity.

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More information

Published date: 28 October 2002
Keywords: translation, elongation factor, mTOR, amino acid, glucose, initiation factor

Identifiers

Local EPrints ID: 56080
URI: http://eprints.soton.ac.uk/id/eprint/56080
ISSN: 0014-2956
PURE UUID: 0f1040f4-09df-4882-81fd-bc58aa5cc3c7

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:31

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Contributors

Author: C.G. Proud

University divisions

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