Beclin 2, a mammal-specific homolog of Beclin 1 with unique functional similarities and differences

Wed, 07/15/2015 - 15:57

Beclin 2 (BECN2) is also called Beclin-1-like protein 1/ BECN1P1 and it was recently identified by He et al 2013 as a mammal-specific homolog of the evolutionarily conserved protein Beclin 1 which is well established for its role in the regulation of autophagy and oncogenic suppression (1). He et al 2013 documented that human Beclin 2 is 57% similar to Beclin 1, and they confirmed its presence in several tissues including brain, placenta, thymus, uterus and skeletal muscles. Further studies from various labs established Beclin-2’s critical role in two distinct lysosomal degradation pathways: as a regulator of autophagy and as a regulator of G-protein coupled receptors/GPCRs turnover. Like Beclin 1, Beclin 2 was also found to regulate autophagy and its effects were demonstrated in basal or starvation-induced autophagy experiments involving bafilomycin A1 and cultured mammalian cells wherein it distinctly reduced the degradation of autophagic substrate p62, the aggregation of a fluorescent form of LC3 into cytoplasmic dots and the lipidation of endogenous LC3 (1, 2). Beclin 2 physically interact with several proteins namely VPS34, ATG14, AMBRA1, BCL2 and UVRAG but not with RUBICON/ KIAA0226, a known BECN1-binding partner and a negative regulator of autophagy, suggesting that Beclin 2 -mediated autophagy is independent of Beclin 1 or RUBICON (2). In an interesting observation, Wei’s lab employed Beclin 2 antibody (NB110- 60984) in WB application on lysates of HeLa cells subjected or not to knockout of BECN1 followed by exogenous expression of BECN1, and demonstrated that the loss of Beclin 1 does not have any effect on Beclin 2 expression (3)

Beclin-2-Antibody-Simple-Western
Beclin 2 Antibody [NB110-60984] - Simple Western lane view shows a specific band for Beclin 2 in 0.5 mg/ml of HeLa lysate. This experiment was performed under reducing conditions using the 12-230 kDa separation system.

Unlike Beclin 1, Beclin 2 specifically interacts/binds with GPCR -associated sorting protein 1 (GASP1 or GPRASP1) and this direct interaction was found to be essential for the agonist-induced lysosomal degradation of GPCRs such as DOR/opioid receptor delta 1 and CB1R/ cannabinoid receptor 1 (1). Beclin 2 has been revealed as a novel regulator of metabolism, obesity and diabetes, and haploinsufficiency of Beclin 2 was observed to lead to increased food intake, obesity and aggravated insulin resistance, which was suggested to be related to enhanced CB1R signaling rather than decreased autophagic activity (1, 4).

Beclin 2 is unique for its mammal-specific presence and its differential roles vs Beclin 1, and it would be exciting to further delineate its functional protein-protein interactions under physiological as well as stress conditions in experiments involving autophagy signaling and mammalian-specific biological functions.

Novus Biologicals offers a variety of Beclin 2 products for your research needs including: Beclin 2 Primary Antibodies Beclin 1/ATG6 Peptides and Proteins

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