What's in the ‘BAG’? – a functional domain analysis of the BAG-family proteins

• Published in: Cancer Letters Vol. 188; no. 1; pp. 25 - 32
• Main Authors: Doong, Howard, Vrailas, Alysia, Kohn, Elise C.
• Format: Book Review Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.12.2002; Elsevier; Elsevier Limited
• Subjects: Amino Acid Sequence; Amino acids; Apoptosis; BcL-2; Biological and medical sciences; Breast cancer; Carcinogenesis, carcinogens and anticarcinogens; Carrier Proteins - chemistry; Cell adhesion & migration; Cell growth; Chaperone; Disease; DNA-Binding Proteins; General aspects; Hsp70; Humans; Insects; Kinases; Medical sciences; Migration; Molecular Sequence Data; Multivariate analysis; NMR; Nuclear magnetic resonance; Pancreatic cancer; Proliferation; Protein Structure, Tertiary; Proteins; Silencer of death domains; Stress response; Studies; Survival; Transcription Factors; Tumors; BcL-2; Silencer of death domains; Hsp70; Migration; Chaperone; Proliferation; Stress response; Survival; Apoptosis; Cell proliferation; Enzyme; Transferases; Review; Malignant tumor; Gene expression; Carcinogenesis; Biological activity; Gene; Structure activity relation; Cell death; Heat shock protein; Onc gene; Protein-tyrosine kinase
• DOI: 10.1016/S0304-3835(02)00456-1
• ISSN: 0304-3835

Bcl-2-associated athanogene (BAG)-family proteins are BAG domain-containing proteins that interact with the heat shock proteins 70, both constitutive Hsc70 and inducible Hsp70. BAG-family proteins bind through the BAG domain to the ATPase domain of Hsc70/Hsp70. The BAG domain, approximately 110 amino acids in length, is a conserved region at the carboxyl terminus and consists of three anti-parallel α helices based on X-ray crystallography and NMR studies. The second and third α-helices of the BAG domain interact with the ATP-binding pocket of Hsc70/Hsp70. Currently, six human BAG proteins have been reported, four of which have been shown to functionally bind Hsc70/Hsp70. BAG-family proteins regulate chaperone protein activities through their interaction with Hsc70/Hsp70. Over-expression of BAG-family proteins is found in several cancers and has been demonstrated in the laboratory to enhance cell survival and proliferation. The anti-apoptotic activities of BAG-family proteins may be dependent on their interactions with Hsc70/Hsp70 and/or binding to Bcl-2. Both BAG-1 and BAG-3/CAIR-1 interact with Bcl-2 and have been shown to have a supra-additive anti-apoptotic effect with Bcl-2. Several N-terminal domains or motifs have been identified in BAG-family proteins as well. These domains enable BAG-family proteins to partner with other proteins and potentially alter the activity of those target proteins by recruiting Hsc70/Hsp70. BAG-family proteins participate in a wide variety of cellular processes including cell survival (stress response), proliferation, migration and apoptosis.