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Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.

The phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) pathway plays pivotal roles in cell survival, growth, and proliferation downstream of growth factors. Its perturbations are associated with cancer progression, type 2 diabetes, and neurological disorders. To better understand the mechanisms of action and regulation of this pathway, we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway. Identification of 67 new interactions was followed by validation by co-affinity purification and exhaustive literature curation of existing information. We provide a nearly complete, functionally annotated interactome of 802 interactions for the PI3K-mTOR pathway. Our screen revealed a predominant place for glycogen synthase kinase-3 (GSK3) A and B and the AMP-activated protein kinase. In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B. Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. We propose that DEAF1 may represent a therapeutic target of lithium and other GSK3 inhibitors used in bipolar disease and depression.

Pubmed ID: 20368287


  • Pilot-Storck F
  • Chopin E
  • Rual JF
  • Baudot A
  • Dobrokhotov P
  • Robinson-Rechavi M
  • Brun C
  • Cusick ME
  • Hill DE
  • Schaeffer L
  • Vidal M
  • Goillot E


Molecular & cellular proteomics : MCP

Publication Data

July 1, 2010

Associated Grants


Mesh Terms

  • Animals
  • Cell Line
  • Glycogen Synthase Kinase 3
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases
  • Promoter Regions, Genetic
  • Protein Interaction Mapping
  • Protein-Serine-Threonine Kinases
  • Proteome
  • Receptor, Serotonin, 5-HT1A
  • Recombinant Fusion Proteins
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Two-Hybrid System Techniques