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Cited by 384

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Regulation of mammalian translation factors by nutrients

Open access
Proud, Christopher G.·2002·European Journal of Biochemistry
DOI 10.1046/j.1432-1033.2002.03292.x
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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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Metadata

Authors
Proud, C. G.
Venue
European Journal of Biochemistry
Publisher
Wiley
Published
2002-10-30
Volume
269
Issue
22
Pages
5338-5349
ISSN
  • 0014-2956 (ISSN-L)
  • 1432-1033
DOI
10.1046/j.1432-1033.2002.03292.x
OpenAlex
W1499618890
Cited by
384
References
6
FWCI
10.48
Type
journal article
Language
en
Open access
bronze

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