A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B
A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B
Eukaryotic initiation factor 2B (eIF2B) plays a key role in controlling the initiation of mRNA translation. eIF2B is heteropentamer whose catalytic () 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 eIF2B. We identify this site as Ser525, located adjacent to the known phosphoregulatory region in eIF2B. 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.
1429-1442
Wang, Xuemin
d6bb4eb2-5687-46ed-b770-cceb22fd792e
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3
March 2008
Wang, Xuemin
d6bb4eb2-5687-46ed-b770-cceb22fd792e
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3
Wang, Xuemin and Proud, Christopher G.
(2008)
A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B.
Molecular and Cellular Biology, 28 (5), .
(doi:10.1128/MCB.01512-07).
(PMID:18160716)
Abstract
Eukaryotic initiation factor 2B (eIF2B) plays a key role in controlling the initiation of mRNA translation. eIF2B is heteropentamer whose catalytic () 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 eIF2B. We identify this site as Ser525, located adjacent to the known phosphoregulatory region in eIF2B. 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.
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e-pub ahead of print date: 26 December 2007
Published date: March 2008
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Local EPrints ID: 155585
URI: http://eprints.soton.ac.uk/id/eprint/155585
ISSN: 0270-7306
PURE UUID: 54cf33de-fc83-48a3-9b2c-bc35a26dee09
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Date deposited: 28 May 2010 08:24
Last modified: 14 Mar 2024 01:39
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Author:
Xuemin Wang
Author:
Christopher G. Proud
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