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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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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. |
format | Online Article Text |
id | pubmed-6013050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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