Interactome mapping of PI3K-mTOR pathway identifies DEAF1 as a new interactor - Archive ouverte HAL
Article Dans Une Revue Molecular and Cellular Proteomics Année : 2010

Interactome mapping of PI3K-mTOR pathway identifies DEAF1 as a new interactor

Résumé

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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Dates et versions

hal-02668075 , version 1 (31-05-2020)

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Citer

Fanny Pilot-Storck, Emilie Chopin, Jean-François Rual, Anaïs Baudot, Pavel Dobrokhotov, et al.. Interactome mapping of PI3K-mTOR pathway identifies DEAF1 as a new interactor. Molecular and Cellular Proteomics, 2010, 9 (7), pp.1578-1593. ⟨10.1074/mcp.M900568-MCP200⟩. ⟨hal-02668075⟩
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