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

Fanny Pilot-Storck 1 Emilie Chopin 1 Jean-François Rual 2 Anaïs Baudot 3 Pavel Dobrokhotov 4 Marc Robinson-Rechavi 4 Christine Brun 5 Michael E Cusick 2 David E. Hill 2 Laurent Schaeffer 1 Marc Vidal 2 Evelyne Goillot 1
1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 CCSB - Center for Cancer Systems Biology
3 Spanish National Cancer Research Centre
4 Département d'Ecologie et d'Evolution
5 TAGC - Technologies avancées pour le génôme et la clinique
Abstract : 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.
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https://hal-ens-lyon.archives-ouvertes.fr/ensl-00817476
Contributor : Agnès Ganivet <>
Submitted on : Wednesday, April 24, 2013 - 4:29:23 PM
Last modification on : Monday, April 8, 2019 - 1:32:04 PM

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  • HAL Id : ensl-00817476, version 1
  • DOI : 10.1074

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ENS-LYON | UNIV-AMU | UNIV-LYON1

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Fanny Pilot-Storck, Emilie Chopin, Jean-François Rual, Anaïs Baudot, Pavel Dobrokhotov, et al.. 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. Molecular and Cellular Proteomics, American Society for Biochemistry and Molecular Biology, 2010, 9, pp.1578-1593. ⟨10.1074⟩. ⟨ensl-00817476⟩

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