4E-BP restrains eIF4E phosphorylation.
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.
['Müller|David|D|', 'Lasfargues|Charline|C|', 'El Khawand|Sally|S|', 'Alard|Amandine|A|', 'Schneider|Robert J|RJ|', 'Bousquet|Corinne|C|', 'Pyronnet|Stéphane|S|', 'Martineau|Yvan|Y|']
eIF4E phosphorylation mTOR 4E-BP1 4E-BP2 MNK1 MNK2