Akt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9113 USA.
Science (Impact Factor: 31.48). 11/2012; 338(6109):956-959. DOI: 10.1126/science.1225967

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.

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