Beclin

Beclin-1, also referred to as Beclin or BECN1, is a conserved protein that functions as a core component of the class III phosphatidylinositol 3-kinase (PI3K-III) complex essential for autophagy. The human BECN1 gene is located on chromosome 17q21. Beclin-1 forms a core complex with the lipid kinase Vps34 (PIK3C3) and the regulatory subunit p150 (VPS15/PIK3R4), and it associates with auxiliary factors such as ATG14L, Ambra1, and UVRAG to initiate autophagosome nucleation.

Beclin-1 contains a BH3 domain and is regulated by interactions with Bcl-2 family proteins; binding of Bcl-2 inhibits autophagy by sequestering Beclin-1. Disruption of this interaction, or post-translational modifications such as phosphorylation by AMPK and DAPK, promotes autophagy. Beclin-1 can also be inhibited by Rubicon. Autophagy proceeds via formation of autophagosomes through the PI3K-III complex, with Beclin-1 playing a key role in membrane nucleation and maturation.

In cancer biology, Beclin-1 is regarded as a haploinsufficient tumor suppressor; monoallelic loss or reduced expression has been observed in several cancers, including breast and ovarian cancers, and Beclin-1–deficient mice show increased tumorigenesis in some models. However, autophagy can have context-dependent roles in cancer, sometimes supporting tumor cell survival.

Beyond autophagy, Beclin-1 participates in endocytic trafficking, innate immunity, and neuronal homeostasis. Ongoing research explores its potential as a therapeutic target in cancer, neurodegenerative diseases, and infectious diseases.