The Beclin-1 (BECN1) gene encodes a 60-kDa coiled-coil protein that interacts with the prototypic apoptosis inhibitor Bcl-2 (1). Beclin-1 promotes autophagy in autophagy-defective yeast with a targeted disruption of agp6/vps30, and in human MCF7 breast carcinoma cells. The autophagy-promoting activity of Beclin-1 in MCF7 cells is associated with inhibition of MCF7 cellular proliferation, in vitro clonigenicity and tumorigenesis. Endogenous Beclin-1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissue, but is expressed ubiquitously at high levels in normal breast epithelia (2). It has also been shown that Beclin 1 contains a leucine-rich nuclear export signal motif raising the possibility that its autophagy and/or tumor suppressor function may require regulated, CRM1-dependent, nucleocytoplasmic transport (3).
Senescence and Autophagy
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