BACKGROUND BAG3 was identified as a co-chaperone of the heat shock protein (Hsp) 70, which helps, through the binding to the ATPase domain, the ADP release from the chaperone and the nucleotide cycling. By interacting with Hsp70, BAG3 modulates the activities of this chaperone, including the delivery of client proteins to proteasome. BAG3 can also carry out Hsp70- independent functions, through its interactions with other proteins involved in apoptosis, cytoskeleton dynamics and other pathways. SCOPE OF REVIEW Here we provide a summary of the main mechanisms which encompass BAG3 as an intracellular factor involved in different pathways which regulate and modulate the physiological cell response. Furthermore, it has been shown that BAG3 can be secreted by some cell types and is able to activate the monocytes through the binding on a membrane cell receptor, indicating that the protein can act like an alarmin with different functions inside and outside the cell. MAJOR CONCLUSIONS Whereas intracellularly BAG3 sustains the levels of anti-apoptotic factors and other molecules, participates in protein quality control, drives the cytoskeleton dynamics, exerts structural and functional roles in myocytes, the discovery of a secreted BAG3 opened a new field of investigation in tumor development and progression, revealing its role in a new signaling pathway, mediated by the BAG3/BAG3R axis, which also includes monocytes and other stromal cells. GENERAL SIGNIFICANCE BAG3 is a multifunctional protein that is involved cell stress response through its participation in several regulatory pathways which control cell homeostatic response in physiological and pathological conditions.

中文翻译：

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BAG3蛋白的多种活性：机制。

背景技术BAG3被鉴定为热休克蛋白（Hsp）70的共同伴侣，它通过与ATPase结构域的结合，帮助ADP从伴侣中释放并促进核苷酸循环。通过与Hsp70相互作用，BAG3调节了该分子伴侣的活性，包括将客户蛋白传递到蛋白酶体上。BAG3还可以通过与细胞凋亡，细胞骨架动力学和其他途径中涉及的其他蛋白质的相互作用来执行Hsp70独立功能。综述范围在这里，我们提供了主要机制的概述，其中包括BAG3作为细胞内因子，参与调节和调节生理细胞应答的不同途径。此外，已经表明，BAG3可以由某些细胞类型分泌，并能够通过与膜细胞受体结合而激活单核细胞，这表明该蛋白可以像报警蛋白一样发挥作用，在细胞内外具有不同的功能。主要结论尽管细胞内BAG3维持抗凋亡因子和其他分子的水平，参与蛋白质质量控​​制，驱动细胞骨架动力学，在心肌细胞中发挥结构和功能作用，但分泌BAG3的发现为肿瘤研究开辟了新的领域BAG3 / BAG3R轴介导了它的发展和进程，揭示了它在新信号通路中的作用，该轴还包括单核细胞和其他基质细胞。