Beclin-1, the mammalian orthologue of yeast Atg6, has a central role in autophagy. It interacts with a number of cofactors to regulate the lipid kinase VPS34 protein and promote formation of Beclin-1-VPS34-p150 core complexes, thereby inducing autophagy. During phagophore formation, the Vps34 complex contains Atg14L, whereas during maturation into an autolysosome in mammals the complex includes UVRAG. Additional modulating proteins in mammalian cells include AMBRA1, BIF1, RUBICON and HMGB1.
The BH3 domain of Beclin-1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin-1, or ubiquitination of Beclin-1. In addition, caspase-mediated cleavage of Beclin-1 promotes crosstalk between apoptosis and autophagy. Beclin-1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration.
應(yīng)用類型
免疫原
Peptide derived from N-terminal region of human beclin-1 protein