The initiation factor eIF4A is involved in the response to lithium stress in Saccharomyces cerevisiae
| Autor: | Domingos C.S. Neto, Mónica Montero-Lomelí, Bruno Leonardo Bozaquel Morais, Daniela L. Figueiredo, Claudio A. Masuda, João R.P. Martins |
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| Rok vydání: | 2002 |
| Předmět: |
Threonine
Saccharomyces cerevisiae Proteins Time Factors Saccharomyces cerevisiae Phosphatase Blotting Western Immunoblotting Lithium Biochemistry chemistry.chemical_compound Nuclear Receptor Coactivator 2 Peptide Initiation Factors Polysome Protein biosynthesis Escherichia coli Phosphoprotein Phosphatases Serine Initiation factor Protein Phosphatase 2 Enzyme Inhibitors Molecular Biology Methionine biology Galactose Cell Biology biology.organism_classification chemistry Phosphoglucomutase Polyribosomes Eukaryotic Initiation Factor-4A Fermentation Carrier Proteins Lithium Chloride Protein Binding Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 277(24) |
| ISSN: | 0021-9258 |
| Popis: | A gene, TIF2, was identified as corresponding to the translation initiation factor eIF4A and when overexpressed it confers lithium tolerance in galactose medium toSaccharomyces cerevisiae. Incubation of yeast with 6 mm LiCl in galactose medium leads to inhibition of [35S]methionine incorporation. By polysome analysis we show that translation is inhibited by lithium at the initiation step, accumulating 80 S monosomes. We further show by immunoblot analysis that when cells are incubated with lithium eIF4A does not sediment with ribosomal subunits. Overexpression of TIF2overcomes 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. |
| Databáze: | OpenAIRE |
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