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Science. 2012 Nov 16;338(6109):956-9. doi: 10.1126/science.1225967. Epub 2012 Oct 25.

Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation.

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  • 1Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

Aberrant signaling through the class I phosphatidylinositol 3-kinase (PI3K)-Akt axis is frequent in human cancer. Here, we show that Beclin 1, an essential autophagy and tumor suppressor protein, is a target of the protein kinase Akt. Expression of a Beclin 1 mutant resistant to Akt-mediated phosphorylation increased autophagy, reduced anchorage-independent growth, and inhibited Akt-driven tumorigenesis. Akt-mediated phosphorylation of Beclin 1 enhanced its interactions with 14-3-3 and vimentin intermediate filament proteins, and vimentin depletion increased autophagy and inhibited Akt-driven transformation. Thus, Akt-mediated phosphorylation of Beclin 1 functions in autophagy inhibition, oncogenesis, and the formation of an autophagy-inhibitory Beclin 1/14-3-3/vimentin intermediate filament complex. These findings have broad implications for understanding the role of Akt signaling and intermediate filament proteins in autophagy and cancer.

Comment in

PMID:
23112296
[PubMed - indexed for MEDLINE]
PMCID:
PMC3507442
Free PMC Article

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