Control of Paip1-eukayrotic translation initiation factor 3 interaction by amino acids through S6 kinase.

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.
Mesh Terms:
Amino Acids, Cell Line, Cell Line, Tumor, Eukaryotic Initiation Factor-3, HEK293 Cells, HeLa Cells, Humans, Peptide Initiation Factors, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, RNA-Binding Proteins, Ribosomal Protein S6 Kinases, 70-kDa, Signal Transduction, TOR Serine-Threonine Kinases
Mol. Cell. Biol.
Date: Mar. 01, 2014
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