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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jennings, Martin D. Zhou, Yu Mohammad-Qureshi, Sarah S. Bennett, David Pavitt, Graham D. |
| Description | Country affiliation: United kingdom Author Affiliation: Jennings MD ( The Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.) |
| Abstract | Protein synthesis factor eIF2 delivers initiator tRNA to the ribosome. Two proteins regulate its G-protein cycle: eIF5 has both GTPase-accelerating protein (GAP) and GDP dissociation inhibitor (GDI) functions, and eIF2B is the guanine nucleotide exchange factor (GEF). In this study, we used protein-protein interaction and nucleotide exchange assays to monitor the kinetics of eIF2 release from the eIF2â¢GDP/eIF5 GDI complex and determine the effect of eIF2B on this release. We demonstrate that eIF2B has a second activity as a GDI displacement factor (GDF) that can recruit eIF2 from the eIF2â¢GDP/eIF5 GDI complex prior to GEF action. We found that GDF function is dependent on the eIF2Bε and eIF2Bγ subunits and identified a novel eIF2-eIF2Bγ interaction. Furthermore, GDF and GEF activities are shown to be independent. First, eIF2B GDF is insensitive to eIF2 phosphorylation, unlike GEF. Second, we found that eIF2Bγ mutations known to disrupt GCN4 translational control significantly impair GDF activity but not GEF function. Our data therefore define an additional step in the protein synthesis initiation pathway that is important for its proper control. We propose a new model to place eIF2B GDF function in the context of efficient eIF2 recycling and its regulation by eIF2 phosphorylation. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.231514.113 |
| Journal | Genes & Development |
| Issue Number | 24 |
| Volume Number | 27 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2013-12-15 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Eukaryotic Initiation Factor-2b Metabolism Eukaryotic Initiation Factors Guanosine Diphosphate Peptide Chain Initiation, Translational Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Genetics Guanine Guanine Nucleotide Dissociation Inhibitors Mutation Phosphorylation Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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