The multiple activities of BAG3 protein: Mechanisms
L Marzullo, MC Turco, M De Marco - Biochimica et Biophysica Acta (BBA) …, 2020 - Elsevier
L Marzullo, MC Turco, M De Marco
Biochimica et Biophysica Acta (BBA)-General Subjects, 2020•ElsevierBackground 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 …
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 …
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.
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