BECN1 Human

Autophagy is a tightly regulated catabolic process where cells under stress sequester cytosolic constituents like damaged proteins and organelles in double-membrane vesicles called autophagosomes . These autophagosomes degrade their cargo by lysosomal proteolysis, generating raw materials for the biosynthesis of vital macromolecules . Beclin 1 is integral to the initial steps in the assembly of autophagosomes from pre-autophagic structures. It is part of the class III phosphatidylinositol 3-kinase complex, which also includes VPS34, VPS15, and ATG14 proteins .

The phosphorylation and ubiquitination of Beclin 1 at various residues fine-tune the responses to diverse autophagy-modulating stimuli, helping maintain the balance between pro-survival autophagy and pro-apoptotic responses . Distinct Beclin 1 phosphorylation events and the diverse signaling pathways and kinases involved play a significant role in the regulation of autophagy .

Beclin 1 is implicated in several diseases, including cancer and neurodegeneration. It plays an important role in tumorigenesis and autophagic programmed cell death . For instance, ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy . Additionally, low levels of Beclin 1 in the hippocampus are associated with schizophrenia, leading to diminished autophagy and increased neuronal cell death .

The first mammalian autophagy-related gene, Beclin 1, was discovered by the Levine group in 1999. They demonstrated that Beclin 1 could restore autophagy activity in autophagy-deficient breast cancer cells . This discovery marked a significant milestone in understanding the molecular mechanisms of autophagy and its implications in human health and disease.