Evidence map›Paper›PMID 20444979›Full record

ArticleMolecular biology of the cell2010

Fusel alcohols regulate translation initiation by inhibiting eIF2B to reduce ternary complex in a mechanism that may involve altering the integrity and dynamics of the eIF2B body.

Eleanor J Taylor, Susan G Campbell, Christian D Griffiths, Peter J Reid, John W Slaven, Richard J Harrison, Paul F G Sims, Graham D Pavitt, Daniela Delneri, Mark P Ashe

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 51 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Eleanor J TaylorFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Susan G Campbell
Christian D Griffiths
Peter J Reid
John W Slaven
Richard J Harrison
Paul F G Sims
Graham D Pavitt
Daniela Delneri
Mark P Ashe
University of Manchester · GBSheffield Hallam University · GBUniversity of Edinburgh · GB

Funding

Biotechnology and Biological Sciences Research CouncilWellcome TrustWellcome Trust 067328/Z/02/ZWellcome Trust 080349/Z/06/Z
6 · The paper itself

Abstract

Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2alpha dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation.

Indexed as

Multiprotein ComplexesAlcoholsBase SequenceEukaryotic Initiation Factor-2BGuanosine DiphosphateGuanosine TriphosphateHumansMolecular Sequence DataMutationProtein BiosynthesisProtein Phosphatase 2Protein SubunitsRecombinant Fusion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAlcoholsEukaryotic Initiation Factor-2Bfusel oilGuanosine DiphosphateGuanosine TriphosphateMultiprotein ComplexesProtein Phosphatase 2Protein SubunitsRecombinant Fusion ProteinsSaccharomyces cerevisiae ProteinsSIT4 protein, S cerevisiae

Identifiers

PMID20444979
PMCPMC2893985
OpenAlexW2102759838

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.