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The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease

The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition...

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Autores principales: Myers, Valerie D., McClung, Joseph M., Wang, JuFang, Tahrir, Farzaneh G., Gupta, Manish K., Gordon, Jennifer, Kontos, Christopher H., Khalili, Kamel, Cheung, Joseph Y., Feldman, Arthur M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013050/
https://www.ncbi.nlm.nih.gov/pubmed/29938246
http://dx.doi.org/10.1016/j.jacbts.2017.09.009
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author Myers, Valerie D.
McClung, Joseph M.
Wang, JuFang
Tahrir, Farzaneh G.
Gupta, Manish K.
Gordon, Jennifer
Kontos, Christopher H.
Khalili, Kamel
Cheung, Joseph Y.
Feldman, Arthur M.
author_facet Myers, Valerie D.
McClung, Joseph M.
Wang, JuFang
Tahrir, Farzaneh G.
Gupta, Manish K.
Gordon, Jennifer
Kontos, Christopher H.
Khalili, Kamel
Cheung, Joseph Y.
Feldman, Arthur M.
author_sort Myers, Valerie D.
collection PubMed
description The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca(2+) channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease.
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spelling pubmed-60130502018-06-21 The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease Myers, Valerie D. McClung, Joseph M. Wang, JuFang Tahrir, Farzaneh G. Gupta, Manish K. Gordon, Jennifer Kontos, Christopher H. Khalili, Kamel Cheung, Joseph Y. Feldman, Arthur M. JACC Basic Transl Sci STATE-OF-THE-ART REVIEW The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca(2+) channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease. Elsevier 2018-03-01 /pmc/articles/PMC6013050/ /pubmed/29938246 http://dx.doi.org/10.1016/j.jacbts.2017.09.009 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle STATE-OF-THE-ART REVIEW
Myers, Valerie D.
McClung, Joseph M.
Wang, JuFang
Tahrir, Farzaneh G.
Gupta, Manish K.
Gordon, Jennifer
Kontos, Christopher H.
Khalili, Kamel
Cheung, Joseph Y.
Feldman, Arthur M.
The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title_full The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title_fullStr The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title_full_unstemmed The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title_short The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease
title_sort multifunctional protein bag3: a novel therapeutic target in cardiovascular disease
topic STATE-OF-THE-ART REVIEW
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013050/
https://www.ncbi.nlm.nih.gov/pubmed/29938246
http://dx.doi.org/10.1016/j.jacbts.2017.09.009
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