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Phosphorylation of eukaryotic initiation factor (eIF) 4E is not required for de novo protein synthesis following recovery from hypertonic stress in human kidney cells
journal contribution
posted on 2023-06-08, 00:20 authored by Simon Morley, Susanne NaegelePrevious work has suggested that increased phosphorylation of eukaryotic initiation factor (eIF) 4E at Ser-209 in the C-terminal loop of the protein often correlates with increased translation rates. However, the functional consequences of phosphorylation have remained contentious with our understanding of the role of eIF4E phosphorylation in translational control far from complete. To investigate the role for eIF4E phosphorylation in de novo translation, we studied the recovery of human kidney cells from hypertonic stress. Results show that hypertonic shock caused a rapid inhibition of protein synthesis and the disaggregation of polysomes. These changes were associated with the dephosphorylation of eIF4G, eIF4E, 4E-binding protein 1 (4E-BP1), and ribosomal protein S6. In addition, decreased levels of the eIF4F complex and increased association of 4E-BP1 with eIF4E were observed over a similar time course. The return of cells to isotonic medium rapidly promoted the phosphorylation of these initiation factors, increased levels of eIF4F complexes, promoted polysome assembly, and increased rates of translation. However, by using a cell-permeable, specific inhibitor of eIF4E kinase, Mnk1 (CGP57380), we show that de novoinitiation of translation and eIF4F complex assembly during this recovery phase did not require eIF4E phosphorylation.
History
Publication status
- Published
Journal
Journal of Biological ChemistryISSN
0021-9258External DOI
Issue
36Volume
277Page range
32855-32859Pages
5.0Department affiliated with
- Biochemistry Publications
Notes
This was the first demonstration that eIF4E phosphorylation is not required for de novo protein synthesis in mammalian cells. SM directed the research, carried out most of the experiments and was the corresponding authorFull text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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