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Bcl-2 Inhibition of Autophagy: A New Route to Cancer?

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas

Requests for reprints: Beth Levine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9113. Phone: 214-648-2202; E-mail: beth.levine{at}utsouthwestern.edu.

Bcl-2 was the first identified cellular protein that functions as an oncogene by blocking apoptotic cell death. Beclin 1, the first identified mammalian autophagy gene product, is a haploinsufficient tumor suppressor that was originally isolated as a Bcl-2-interacting protein. We recently showed that Bcl-2 negatively regulates Beclin 1-dependent autophagy and Beclin 1-dependent autophagic cell death. These findings raise the possibility that Bcl-2 family members may function as oncogenes not only by blocking apoptosis but also by blocking autophagy. (Cancer Res 2006; 66(6): 2885-8)

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