ABSTRACT
Beclin 1 acts as a tumor suppressor and is an essential mediator of autophagy. Beclin 1 also interacts with Bcl-2 and can induce apoptosis by activating the mitochondrion permeabilizing function of proapoptotic multidomain proteins from the Bcl-2 family. Moreover, these Bcl-2 family members can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-XL at the level of the endoplasmic reticulum. We found that overexpression of Beclin 1 in U87 glioblastoma cells enhanced the capacity for cellular autophagy and induced apoptosis. Silencing of Beclin 1 decreased autophagic capacity but had little effect on apoptosis and cell proliferation. Beclin 1-Bcl-2 and Beclin 1-Bcl-xL complexes were detected by immunoprecipitation in cells that overexpressed Beclin 1. Furthermore, the levels of cytochrome c in the cytosol and the activity of caspases-3/-9 in the cytosol increased after overexpression of Beclin 1. Our results suggest that Beclin 1 induces apoptosis via binding to Bcl-2 and Bcl-xL, followed by the release of cytochrome c into the cytosol and activation of caspases-3/-9.
