4E-BP restrains eIF4E phosphorylation

Translation
David MüllerYvan Martineau

Abstract

In eukaryotes, mRNA translation is dependent on the cap-binding protein eIF4E. Through its simultaneous interaction with the mRNA cap structure and with the ribosome-associated eIF4G adaptor protein, eIF4E physically posits the ribosome at the 5' extremity of capped mRNA. eIF4E activity is regulated by phosphorylation on a unique site by the eIF4G-associated kinase MNK. eIF4E assembly with the eIF4G-MNK sub-complex can be however antagonized by the hypophosphorylated forms of eIF4E-binding protein (4E-BP). We show here that eIF4E phosphorylation is dramatically affected by disruption of eIF4E-eIF4G interaction, independently of changes in MNK expression. eIF4E phosphorylation is actually strongly downregulated upon eIF4G shutdown or upon sequestration by hypophosphorylated 4E-BP, consequent to mTOR inhibition. Downregulation of 4E-BP renders eIF4E phosphorylation insensitive to mTOR inhibition. These data highlight the important role of 4E-BP in regulating eIF4E phosphorylation independently of changes in MNK expression.

References

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Citations

Apr 23, 2016·Viruses·Elizabeth Royall, Nicolas Locker
Jun 28, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Muhammad Umar AliCao Jiang
Dec 16, 2017·Molecular and Cellular Biochemistry·Kama E Szereszewski, Kenneth B Storey
Dec 16, 2018·International Journal of Biological Macromolecules·Asiya BatoolKhurshid Iqbal Andrabi

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Methods Mentioned

BETA
immunoprecipitation
FCS
Protein Assay

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