The Initiation Factor eIF4A Is Involved in the Response to Lithium Stress in Saccharomyces cerevisiae

A gene, TIF2, was identified as corresponding to the translation initiation factor eIF4A and when overexpressed it confers lithium tolerance in galactose medium to Saccharomyces cerevisiae . Incubation of yeast with 6 m m LiCl in galactose medium leads to inhibition of [ 35 S]methionine incorporatio...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 277; no. 24; pp. 21542 - 21548
Main Authors:	Montero-Lomeli, Monica, Morais, Bruno L B, Figueiredo, Daniela L, Neto, Domingos C S, Martins, João R P, Masuda, Claudio A
Format:	Journal Article
Language:	English
Published:	United States American Society for Biochemistry and Molecular Biology 14-06-2002
Subjects:	Blotting, Western Carrier Proteins - physiology Enzyme Inhibitors - pharmacology Escherichia coli - metabolism Eukaryotic Initiation Factor-4A Fermentation - drug effects Galactose - pharmacology Immunoblotting initiation factor eIF-4A Lithium - pharmacology Lithium Chloride - pharmacology Nuclear Receptor Coactivator 2 Peptide Initiation Factors - physiology Phosphoglucomutase - antagonists & inhibitors Phosphoprotein Phosphatases Polyribosomes - metabolism Protein Binding Protein Phosphatase 2 Saccharomyces cerevisiae Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Serine - metabolism SIT4 gene Threonine - metabolism TIF2 gene Time Factors Transcription Factors - physiology
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Summary:	A gene, TIF2, was identified as corresponding to the translation initiation factor eIF4A and when overexpressed it confers lithium tolerance in galactose medium to Saccharomyces cerevisiae . Incubation of yeast with 6 m m LiCl in galactose medium leads to inhibition of [ 35 S]methionine incorporation. By polysome analysis we show that translation is inhibited by lithium at the initiation step, accumulating 80âS monosomes. We further show by immunoblot analysis that when cells are incubated with lithium eIF4A does not sediment with ribosomal subunits. Overexpression of TIF2 overcomes inhibition of protein synthesis and restores its sedimentation with the initiation complex. In vivo , eIF4A is induced by lithium stress. We have shown previously that lithium is highly toxic to yeast when grown in galactose medium mainly due to inhibition of phosphoglucomutase, an enzyme responsible for the entry of galactose into glycolysis. We show that conditions that revert inhibition of phosphoglucomutase also revert inhibition of protein synthesis. Interestingly, glucose starvation leads to loss of polysomes but not to dissociation of eIF4A from the preinitiation complexes. Overexpression of SIT4 , a protein phosphatase related to the TOR kinase pathway, reverts inhibition of protein synthesis by lithium and association of eIF4A with the initiation complex.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.M201977200