Bcl-2-associated athanogene 2 (BAG2)

Bcl-2-associated athanogene 2 (BAG2) is a multifunctional co-chaperone and a member of the BAG family, characterized by a conserved C-terminal BAG domain [1, 10]. It primarily acts as a nucleotide exchange factor (NEF) for the molecular chaperones Hsp70 and Hsc70, facilitating the release of ADP and client proteins to regulate protein folding and quality control [1, 4]. Beyond its NEF activity, BAG2 serves as a potent inhibitor of the E3 ubiquitin ligase CHIP (Carboxyl-terminus of Hsp70-interacting protein), thereby preventing the proteasomal degradation of various substrates, including mutant p53, PINK1, and STING [1, 5, 17]. In oncology, BAG2 is frequently overexpressed and associated with poor prognosis, as it stabilizes oncogenic proteins and suppresses apoptosis in cancers such as hepatocellular carcinoma and breast cancer [8, 11]. It is also implicated in neurodegenerative disorders like Parkinson's and Alzheimer's diseases through its role in managing protein aggregates like Tau [1, 4, 16]. Recent research has identified BAG2 as a therapeutic target in keloid disease and certain malignancies, with small molecules such as bazedoxifene and ponesimod demonstrating high binding affinity and inhibitory potential [6, 9].

Other names

BAG-2BAG family molecular chaperone regulator 2BAG cochaperone 2dJ417I1.2

BAG2 acts as a nucleotide exchange factor (NEF) for Hsp70/Hsc70, promoting the release of ADP and client proteins [1, 4]. It also inhibits the E3 ubiquitin ligase CHIP, thereby preventing the ubiquitination and degradation of specific substrates [1, 3, 5].