Translation Elongation Factor 1A Mutants with Altered Actin Bundling Activity Show Reduced Aminoacyl-tRNA Binding and Alter Initiation via eIF2α Phosphorylation
| Autor: | Terri Goss Kinzy, Winder B. Perez |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Eukaryotic Initiation Factor-2 Peptide Chain Elongation Translational macromolecular substances Saccharomyces cerevisiae Protein Serine-Threonine Kinases RNA Transfer Amino Acyl Biology Biochemistry Peptide Elongation Factor 1 Eukaryotic translation Eukaryotic initiation factor Prokaryotic translation Initiation factor Actin-binding protein Phosphorylation Molecular Biology eIF2 RNA Fungal Cell Biology Actin cytoskeleton Actins Eukaryotic translation elongation factor 1 alpha 1 Cell biology Protein Synthesis and Degradation Mutation biology.protein Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 289:20928-20938 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.570077 |
| Popis: | Apart from its canonical function in translation elongation, eukaryotic translation elongation factor 1A (eEF1A) has been shown to interact with the actin cytoskeleton. Amino acid substitutions in eEF1A that reduce its ability to bind and bundle actin in vitro cause improper actin organization in vivo and reduce total translation. Initial in vivo analysis indicated the reduced translation was through initiation. The mutant strains exhibit increased levels of phosphorylated initiation factor 2α (eIF2α) dependent on the presence of the general control non-derepressible 2 (Gcn2p) protein kinase. Gcn2p causes downregulation of total protein synthesis at initiation in response to increases in deacylated tRNA levels in the cell. Increased levels of eIF2α phosphorylation are not due to a general reduction in translation elongation as eEF2 and eEF3 mutants do not exhibit this effect. Deletion of GCN2 from the eEF1A actin bundling mutant strains revealed a second defect in translation. The eEF1A actin-bundling proteins exhibit changes in their elongation activity at the level of aminoacyl-tRNA binding in vitro. These findings implicate eEF1A in a feedback mechanism for regulating translation at initiation. |
| Databáze: | OpenAIRE |
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