Gene interactions and pathways from curated databases and text-mining
Cell 2005, PMID: 16286006

mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events.

Holz, Marina K; Ballif, Bryan A; Gygi, Steven P; Blenis, John

In response to nutrients, energy sufficiency, hormones, and mitogenic agents, S6K1 phosphorylates several targets linked to translation. However, the molecular mechanisms whereby S6K1 is activated, encounters substrate, and contributes to translation initiation are poorly understood. We show that mTOR and S6K1 maneuver on and off the eukaryotic initiation factor 3 (eIF3) translation initiation complex in a signal-dependent, choreographed fashion. When inactive, S6K1 associates with the eIF3 complex, while the S6K1 activator mTOR/raptor does not. Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and phosphorylation of S6K1 at its hydrophobic motif. Phosphorylation results in S6K1 dissociation, activation, and subsequent phosphorylation of its translational targets, including eIF4B, which is then recruited into the complex in a phosphorylation-dependent manner. Thus, the eIF3 preinitiation complex acts as a scaffold to coordinate a dynamic sequence of events in response to stimuli that promote efficient protein synthesis.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: EIF3C — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3B — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3C — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3B — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4B — EIF3B (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3B — RPS6 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3H — RPS6KB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3C — RPS6KB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3B — RPS6KB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3F — RPS6KB1 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: Complex of MTOR-EIF3B-RPTOR-RPTOR-EIF3B-MTOR-EIF3B-MTOR-RPTOR (in vivo)
  • IRef Hprd Interaction: Complex of EIF3B-EIF3C-RPS6KB1-EIF3B-EIF3C-RPS6KB1-EIF3C-RPS6KB1-EIF3B (in vivo)
  • IRef Innatedb Interaction: EIF3B — MTOR (unknown, -)
  • IRef Innatedb Interaction: EIF4B — EIF3B (unknown, -)
  • IRef Innatedb Interaction: EIF3B — RPS6KB1 (unknown, -)
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → eIF3/p70S6K complex (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → p70S6K (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: eIF3/p70S6K complex (RPS6KB1) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 18 gene pairs are associated to this article in curated databases