Doong Howard, Vrailas Alysia, Kohn Elise C
Molecular Signaling Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancer Lett. 2002 Dec 15;188(1-2):25-32. doi: 10.1016/s0304-3835(02)00456-1.
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 alpha helices based on X-ray crystallography and NMR studies. The second and third alpha-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.
Bcl-2相关抗凋亡基因（BAG）家族蛋白是一类含有BAG结构域的蛋白质，可与组成型热休克蛋白70（Hsc70）和诱导型热休克蛋白70（Hsp70）相互作用。BAG家族蛋白通过BAG结构域与Hsc70/Hsp70的ATP酶结构域结合。BAG结构域长度约为110个氨基酸，是位于羧基末端的保守区域，根据X射线晶体学和核磁共振研究，它由三个反平行的α螺旋组成。BAG结构域的第二个和第三个α螺旋与Hsc70/Hsp70的ATP结合口袋相互作用。目前，已报道了六种人类BAG蛋白，其中四种已被证明在功能上可与Hsc70/Hsp70结合。BAG家族蛋白通过与Hsc70/Hsp70相互作用来调节伴侣蛋白的活性。在几种癌症中发现了BAG家族蛋白的过表达，并且在实验室中已证明其可增强细胞存活和增殖。BAG家族蛋白的抗凋亡活性可能取决于它们与Hsc70/Hsp70的相互作用和/或与Bcl-2的结合。BAG-1和BAG-3/CAIR-1均与Bcl-2相互作用，并且已证明与Bcl-2具有超加成抗凋亡作用。在BAG家族蛋白中还鉴定出了几个N端结构域或基序。这些结构域使BAG家族蛋白能够与其他蛋白结合，并可能通过募集Hsc70/Hsp70来改变那些靶蛋白的活性。BAG家族蛋白参与多种细胞过程，包括细胞存活（应激反应）、增殖、迁移和凋亡。
