Gene interactions and pathways from curated databases and text-mining
Cell 2009, PMID: 19446321

DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival.

Peterson, Timothy R; Laplante, Mathieu; Thoreen, Carson C; Sancak, Yasemin; Kang, Seong A; Kuehl, W Michael; Gray, Nathanael S; Sabatini, David M

The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2. Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities. DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt. Consistent with many human cancers having activated mTORC1 and mTORC2 pathways, DEPTOR expression is low in most cancers. Surprisingly, DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB translocations. In these cells, high DEPTOR expression is necessary to maintain PI3K and Akt activation and a reduction in DEPTOR levels leads to apoptosis. Thus, we identify a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival.

Diseases/Pathways annotated by Medline MESH: Multiple Myeloma
Document information provided by NCBI PubMed

Text Mining Data

S6K1 ⊣ DEPTOR: " Loss of DEPTOR activates S6K1 , Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities "

SGK1 ⊣ DEPTOR: " Loss of DEPTOR activates S6K1, Akt, and SGK1 , promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities "

mTORC1 ⊣ DEPTOR: " Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities "

mTORC2 ⊣ DEPTOR: " Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities "

Akt ⊣ DEPTOR: " Loss of DEPTOR activates S6K1, Akt , and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities "

S6K1 ⊣ DEPTOR: " DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt "

Akt → DEPTOR: " DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt "

Manually curated Databases

  • IRef Biogrid Interaction: RICTOR — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MLST8 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1S1 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RICTOR — DEPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: METAP2 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: DEPTOR — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1S1 — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPTOR — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: DEPTOR — RPTOR (physical association, affinity chromatography technology)
  • IRef Intact Interaction: Complex of MLST8-DEPTOR-DEPTOR-MLST8 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: DEPTOR — MTOR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of DEPTOR-MTOR-RPTOR-RPTOR-DEPTOR-MTOR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RPTOR-AKT1S1-MTOR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of DEPTOR-MTOR-DEPTOR-RICTOR-MTOR-RICTOR (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of 17 proteins (physical association, anti bait coimmunoprecipitation)
  • NCI Pathway Database mTOR signaling pathway: DEPTOR (DEPTOR) → mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: DEPTOR (DEPTOR) → mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) → mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) → TSC1/TSC2 complex (TSC1-TSC2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → DEPTOR (DEPTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → PRAS40 (AKT1S1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: AKT1 (AKT1) → RHEB/GTP complex (RHEB) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: AKT1 (AKT1) → mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: AKT1 (AKT1) → DEPTOR (DEPTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: AKT1 (AKT1) → PRAS40 (AKT1S1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: RHEB/GTP complex (RHEB) → mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: RHEB/GTP complex (RHEB) → DEPTOR (DEPTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: RHEB/GTP complex (RHEB) → PRAS40 (AKT1S1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) → DEPTOR (DEPTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) → PRAS40 (AKT1S1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: DEPTOR (DEPTOR) → PRAS40 (AKT1S1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 56 gene pairs are associated to this article in curated databases