title: Control of Paip1-eukayrotic translation initiation factor 3 interaction by amino acids through S6 kinase.
abstract: The simultaneous interaction of poly(A)-binding protein (PABP) with eukaryotic translation initiation factor 4G (eIF4G) and the mRNA 3' poly(A) tail promotes translation initiation. We previously showed that the interaction of PABP-interacting protein 1 (Paip1) with PABP and eukaryotic translation initiation factor 3 (eIF3; via the eIF3g subunit) further stimulates translation. Here, we demonstrate that the interaction of eIF3 with Paip1 is regulated by amino acids through the mTORC1 signaling pathway. The Paip1-eIF3 interaction is impaired by the mTORC1 inhibitors, rapamycin and PP242. We show that ribosomal protein S6 kinases 1 and 2 (S6K1/2) promote the interaction of eIF3 with Paip1. The enhancement of Paip1-eIF3 interaction by amino acids is abrogated by an S6K inhibitor or shRNA against S6K1/2. S6K1 interacts with eIF3f and, in vitro, phosphorylates eIF3. Finally, we show that S6K inhibition leads to a reduction in translation by Paip1. We propose that S6K1/2 phosphorylate eIF3 to stimulate Paip1-eIF3 interaction and consequent translation initiation. Taken together, these data demonstrate that eIF3 is a new translation target of the mTOR/S6K pathway.
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Martineau
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Wang
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Petroulakis
authors.forename: David
authors.initials: D
authors.lastname: Shahbazian
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fabre
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Bousquet-Dubouch
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pyronnet
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000596:Amino Acids; D039621:Eukaryotic Initiation Factor-3; C111580:PAIP1 protein, human; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1