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

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          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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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Nov 16 2012
          : 338
          : 6109
          Affiliations
          [1 ] Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
          Article
          science.1225967 NIHMS421265
          10.1126/science.1225967
          3507442
          23112296
          9042ba2b-3986-45ec-8dac-4994b510bfcf
          History

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