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Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15370-5. Epub 2004 Oct 18.

Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt.

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  • 1Institute for Systems Biology, Seattle, WA 98103, USA.


beta-Catenin is a central effector of Wnt signaling in embryonic and stem cell development and in tumorigenesis. Here, through a mass spectrometric analysis of a beta-catenin protein complex, we identified 12 proteins as putative beta-catenin interactors. We show that one of them, 14-3-3zeta, enhances beta-catenin-dependent transcription by maintaining a high level of beta-catenin protein in the cytoplasm. More importantly, 14-3-3zeta facilitates activation of beta-catenin by the survival kinase Akt and colocalizes with activated Akt in intestinal stem cells. We propose that Akt phosphorylates beta-catenin, which results in 14-3-3zeta binding and stabilization of beta-catenin, and these interactions may be involved in stem cell development.

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