| Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of proteins activated in response to nutrient deprivation and in neurodegenerative conditions (1). One of the proteins critical to this process is Beclin-1, the mammalian orthologue of the yeast autophagy protein Apg6/Vps30 (2). Beclin-1 can complement defects in yeast autophagy caused by loss of Apg6 and can also stimulate autophagy when overexpressed in mammalian cells (3). Mammalian Beclin-1 was originally isolated in a yeast two-hybrid screen for Bcl-2 interacting proteins and has been shown to interact with Bcl-2 and Bcl-xL but not with Bax or Bak (4). While Beclin-1 is generally ubiquitously expressed, it is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers (5). It is localized within cytoplasmic structures including the mitochondria, although overexpression of Beclin-1 reveals some nuclear staining and CRM1-dependent nuclear export (6). Beclin-1 -/- mice die early in embryogenesis and Beclin-1 -/+ mice have a high incidence of spontaneous tumors. Stem cells from the null mice demonstrate an altered autophagic response although responses to apoptosis appeared normal (7). Overexpression of Beclin-1 in virally infected neurons in vivo resulted in significant protection against Sindbis virus-induced disease and neuronal apoptosis (4). |
