Beclin 1 (human, recombinant)

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.³

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1. Parzych, K.R., and Klionsky, D.J. An overview of autophagy: Morphology, mechanism, and regulation. Antioxid. Redox Signal. 20(3), 460-473 (2014).

2. Furuya, N., Yu, J., Byfield, M., et al. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1(1), 46-52 (2005).

3. Cao, Y., and Klionsky, D.J. Physiological functions of Atg6/Beclin 1: A unique autophagy-related protein. Cell Res. 17(10), 839-849 (2007).

4. Burman, C., and Ktistakis, N.T. Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett. 584(7), 1302-1312 (2010).

5. Pickford, D., Masliah, E., Britschgi, M., et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J. Clin. Invest. 118(6), 2190-2199 (2008).