Beclin 1 (BECN1) is a core component of the class III phosphatidylinositol 3-kinase (PI3K) complex, which generates phosphatidylinositol 3-phosphate (PI3P) and has functions in macroautophagy and the endocytic pathway when associated with ATG14 and UVRAG, respectively.1 BECN1 is comprised of a BH3 domain involved in Bcl-2/Bcl-xL binding, a coiled-coil domain, and an evolutionarily conserved domain (ECD) that is required for association with the PI3K complex.2,3 Binding of BECN1 to various BECN1-interacting proteins can regulate the activity of the ATG14-containing PI3K complex, which is required for nucleation of the phagophore during macroautophagy.1,4 Binding of the anti-apoptotic protein Bcl-2 to BECN1 prevents the association of BECN1 with the PI3K complex and inhibits autophagy, whereas AMBRA1, which also binds directly to BECN1, positively regulates the PI3K complex to facilitate autophagy.1,3 Transfection of autophagy-deficient MCF-7 human breast cancer cells with wild-type BECN1, but not a BECN1 mutant lacking the ECD, increases starvation-induced autophagy in vitro and inhibits tumor growth in an MCF-7 mouse xenograft model, indicating that BECN1 has ECD-dependent tumor suppressor activity.2 BECN1 heterozygous mice expressing human amyloid precursor protein (APP+Becn1+/- mice) have decreased autophagy in the cerebral cortex, increased extracellular amyloid-β (Aβ) deposits in the frontal cortex, and increased intraneuronal Aβ accumulation in the hippocampus and frontoparietal cortex compared to APP+Becn1+/+ mice.5 BECN1 may also have roles in ischemia/reperfusion injury, Niemann-Pick type C disease, and protection against viral infection.3WARNING This product is not for human or veterinary use.
