Editors' ChoiceCell Biology

Getting Autophagy to Akt

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Sci. Signal.  20 Nov 2012:
Vol. 5, Issue 251, pp. ec301
DOI: 10.1126/scisignal.2003784

The protein kinase Akt is often activated in human cancers and is thought to promote tumor formation. One way in which it may do so is by inhibiting autophagy (a process by which the cell digests its own proteins or organelles, especially damaged ones). Wang et al. (see the Perspective by Koren and Kimchi) provide a direct molecular mechanism by which Akt regulates autophagy. Beclin, a component of the autophagy machinery, appears to be a direct target of phosphorylation by Akt. Such phosphorylation enhanced interaction of Beclin with intermediate filaments of the cytoskeleton and inhibited autophagy. Expression of a modified Beclin 1 molecule that could not be phosphorylated by Akt inhibited Akt-induced transformation of cells in culture and tumor formation in a mouse model.

R. C. Wang, Y. Wei, Z. An, Z. Zou, G. Xiao, G. Bhagat, M. White, J. Reichelt, B. Levine, Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science 338, 956–959 (2012). [Abstract] [Full Text]

I. Koren, A. Kimchi, Promoting tumorigenesis by suppressing autophagy. Science 338, 889–890 (2012). [Abstract] [Full Text]