Autophagy, the process of bulk degradation of cellular proteins through an autophagosomic-lysosomal pathway is important for normal growth control and may be defective in tumor cells. Beclin-1, a coiled-coil Bcl-2-interacting protein homologous to the yeast autophagy gene apg6, is a mammalian autophagy gene that can inhibit tumorigenesis and is expressed at reduced levels in human breast carcinoma, suggesting that defects in autophagy proteins may contribute to the development or progression of tumors. Bcl-2 can bind to Beclin-1 and inhibit Beclin-1-dependent autophagy in yeast and mammalian cells, suggesting that Bcl-2 functions as an anti-autophagy protein as well as an anti-apoptotic protein, which helps maintain autophagy at levels that are more compatible with cell survival rather than cell death. ULK1 protein kinase and the VPS34 lipid kinase are key regulators of autophagy initiation and progression. Activated during low nutrient conditions, ULK1 directly phosphorylates Beclin-1 at multiple sites including Ser15.
