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.

Details

Serval ID
serval:BIB_99B5C8832AB6
Type
Article: article from journal or magazin.
Collection
Publications
Title
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.
Journal
Molecular and Cellular Proteomics
Author(s)
Pilot-Storck F., Chopin E., Rual J.F., Baudot A., Dobrokhotov P., Robinson-Rechavi M., Brun C., Cusick M.E., Hill D.E., Schaeffer L., Vidal M., Goillot E.
ISSN
1535-9484[electronic], 1535-9476[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
9
Number
7
Pages
1578-1593
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
07/04/2010 9:30
Last modification date
20/08/2019 16:01
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