TAILIEUCHUNG - Báo cáo Y học: Regulation of mammalian translation factors by nutrients

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 pro-tein 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. Anumber of components of the translational machinery are regulated through signalling events that require the mam-malian target of rapamycin, mTOR. . | Eur. J. Biochem. 269 5338-5349 2002 FEBS 2002 doi MINIREVIEW Regulation of mammalian translation factors by nutrients Christopher G. Proud Division of Molecular Physiology School of Life Sciences University of Dundee MSI WTB Complex Dow Street UK 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 .

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