title: 4E-BP restrains eIF4E phosphorylation.
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.
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Müller
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: Charline
authors.initials: C
authors.lastname: Lasfargues
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: Sally
authors.initials: S
authors.lastname: El Khawand
authors.affiliation: New York University School of Medicine; New York, NY USA.
authors.forename: Amandine
authors.initials: A
authors.lastname: Alard
authors.affiliation: New York University School of Medicine; New York, NY USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schneider
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bousquet
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pyronnet
authors.affiliation: INSERM UMR-1037; Toulouse University; Cancer Research Center of Toulouse (CRCT); Equipe Labellisée Ligue Contre le Cancer and Laboratoire d'Excellence Toulouse Cancer (TOUCAN); Toulouse, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Martineau
keywords: 4E-BP1; 4E-BP2; MNK1; MNK2; eIF4E; mTOR; phosphorylation
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