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Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease
Jonathan A. Kirk, … , Joseph Y. Cheung, Arthur M. Feldman
Jonathan A. Kirk, … , Joseph Y. Cheung, Arthur M. Feldman
Published August 16, 2021
Citation Information: J Clin Invest. 2021;131(16):e149415. https://doi.org/10.1172/JCI149415.
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Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease

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Abstract

Bcl2-associated athanogene-3 (BAG3) is expressed ubiquitously in humans, but its levels are highest in the heart, the skeletal muscle, and the central nervous system; it is also elevated in many cancers. BAG3’s diverse functions are supported by its multiple protein-protein binding domains, which couple with small and large heat shock proteins, members of the Bcl2 family, other antiapoptotic proteins, and various sarcomere proteins. In the heart, BAG3 inhibits apoptosis, promotes autophagy, couples the β-adrenergic receptor with the L-type Ca2+ channel, and maintains the structure of the sarcomere. In cancer cells, BAG3 binds to and supports an identical array of prosurvival proteins, and it may represent a therapeutic target. However, the development of strategies to block BAG3 function in cancer cells may be challenging, as they are likely to interfere with the essential roles of BAG3 in the heart. In this Review, we present the current knowledge regarding the biology of this complex protein in the heart and in cancer and suggest several therapeutic options.

Authors

Jonathan A. Kirk, Joseph Y. Cheung, Arthur M. Feldman

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Figure 1

Structure and function of BAG3.

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Structure and function of BAG3.
Binding sites on BAG3 are shown in yello...
Binding sites on BAG3 are shown in yellow, and their binding partners are shown in purple. Posttranslational modifications (specifically phosphorylation) are indicated vertically.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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