Home LiteratureArticle Details
PMID: 11707417 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel eIF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols.

The EMBO journal ·Vol. 20 ·No. 22 ·2001-11-15 ·Pages 6464-74

Ashe MP, Slaven JW, De Long SK, Ibrahimo S, Sachs AB

Abstract

Fusel alcohols are natural products of amino acid catabolism in the yeast Saccharomyces cerevisiae that cause morphological changes similar to those seen during pseudohyphal growth. We have discovered that certain of these alcohols, including butanol and isoamyl alcohol, bring about a rapid inhibition of translation at the initiation step. This inhibition is strain specific and is not explained by previously described translational control pathways. Using genetic mapping, we have identified a proline to serine allelic variation at amino acid 180 of the GCD1 gene product as the genetic locus that allows translational regulation upon butanol addition. Gcd1p forms part of the eIF2B guanine nucleotide complex that is responsible for recycling eIF2-GDP to eIF2-GTP. This represents one of the key limiting steps of translation initiation and we provide evidence that fusel alcohols target eIF2B in order to bring about translational regulation.

MeSH Terms
Alcohols/metabolism Alleles Butanols/pharmacology Chromosome Mapping Diploidy Eukaryotic Initiation Factor-2B/metabolism Evolution, Molecular Genes, Reporter Genetic Variation Guanine/metabolism Immunoblotting Lac Operon Meiosis Methionine/metabolism Models, Biological Pentanols/pharmacology Phenotype Phosphorylation Plasmids/metabolism Precipitin Tests Proline/genetics Protein Biosynthesis Protein Kinases/metabolism Protein Serine-Threonine Kinases Ribosomes/metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins Serine/chemistry,genetics Sucrose/pharmacology Time Factors beta-Galactosidase/metabolism
Chemicals
Alcohols Butanols Eukaryotic Initiation Factor-2B Pentanols Saccharomyces cerevisiae Proteins fusel oil Serine Sucrose Guanine Proline Methionine isopentyl alcohol Protein Kinases GCN2 protein, S cerevisiae Protein Serine-Threonine Kinases beta-Galactosidase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ashe M P
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK. [email protected]
Slaven J W
De Long S K
Ibrahimo S
Sachs A B
References (20)
20 references, click to expand
  1. Translation initiation: adept at adapting.
    Trends Biochem Sci. 1999 Oct;24(10):398-403 PMID: 10500305
  2. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase.
    Nature. 1999 Jan 21;397(6716):271-4 PMID: 9930704
  3. Glucose depletion rapidly inhibits translation initiation in yeast.
    Mol Biol Cell. 2000 Mar;11(3):833-48 PMID: 10712503
  4. Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation.
    Mol Cell Biol. 2000 Jun;20(11):3965-76 PMID: 10805739
  5. L-leucine availability regulates phosphatidylinositol 3-kinase, p70 S6 kinase and glycogen synthase kinase-3 activity in L6 muscle cells: evidence for the involvement of the mammalian target of rapamycin (mTOR) pathway in the L-leucine-induced up-regulation of system A amino acid transport.
    Biochem J. 2000 Sep 1;350 Pt 2:361-8 PMID: 10947949
  6. Alterations of transcription and translation in HeLa cells exposed to amino acid analogs.
    Mol Cell Biol. 1984 Jun;4(6):1063-72 PMID: 6610822
  7. Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Jul;4(7):1326-33 PMID: 6095062
  8. Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast.
    Cell. 1992 Feb 7;68(3):585-96 PMID: 1739968
  9. A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast.
    Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 PMID: 8506384
  10. TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin.
    Cell. 1995 Jul 14;82(1):121-30 PMID: 7606777
  11. Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes.
    Mol Cell Biol. 1995 Nov;15(11):6351-63 PMID: 7565788
  12. Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs.
    Protein Sci. 1995 Aug;4(8):1608-17 PMID: 8520487
  13. 'Fusel' alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts.
    Microbiology. 1996 Jun;142 ( Pt 6):1391-7 PMID: 8704979
  14. TOR controls translation initiation and early G1 progression in yeast.
    Mol Biol Cell. 1996 Jan;7(1):25-42 PMID: 8741837
  15. A 13C nuclear magnetic resonance investigation of the metabolism of leucine to isoamyl alcohol in Saccharomyces cerevisiae.
    J Biol Chem. 1997 Oct 24;272(43):26871-8 PMID: 9341119
  16. Molecular mechanisms for the control of translation by insulin.
    Biochem J. 1997 Dec 1;328 ( Pt 2):329-41 PMID: 9371685
  17. Bidirectional modulation of insulin action by amino acids.
    J Clin Invest. 1998 Apr 1;101(7):1519-29 PMID: 9525995
  18. An investigation of the metabolism of valine to isobutyl alcohol in Saccharomyces cerevisiae.
    J Biol Chem. 1998 Oct 2;273(40):25751-6 PMID: 9748245
  19. Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling.
    J Biol Chem. 1998 Oct 23;273(43):28178-84 PMID: 9774438
  20. Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae.
    Mol Biol Cell. 2000 Jan;11(1):183-99 PMID: 10637301
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.22.6464
Email
[email protected]
Published
2001-11-15
Pages
6464-74
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125737
Subset
IM
Grants
NIGMS NIH HHS · GM50308 · United States
External Links
PubMed source DOI: 10.1093/emboj/20.22.6464 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2