ArticleThe Journal of clinical investigation2017
Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 136 citations in OpenAlex.
- Depletion of BIS in astrocytes aggravates reactive gliosis following photothrombotic brain injury.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- C-terminal extension of HSPB6 in a family with myopathy and cataract.Human molecular genetics · 2026Article
- Atorvastatin Protects Against Deleterious Carfilzomib-Induced Transcriptional Changes in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2026Article
- Disrupted Sarcomere Reorganization of Cardiomyopathy-Prone Human iPSC-Derived Cardiomyocytes on a Dynamic Mechanical Substrate.Cellular and molecular bioengineering · 2025Article
- Unraveling the Role of BAG3 in Hepatic Fibrosis: Genetic and Biomarker Insights in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).International journal of molecular sciences · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging.Aging cell · 2025Article
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- The BAG3-HSP70-CHIP axis controls the degradation of TGFBR2 in cardiac fibroblasts.Journal of molecular and cellular cardiology · 2025Article
- Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease.Science advances · 2025Article
- Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.The Journal of clinical investigation · 2025Article
- Cardiogenic Shock in a Young South Asian Male With Cardiomyopathy due to a Pathogenic Variant of BAG3 Gene.Case reports in medicine · 2025Article
- Targeting calpain-2-mediated junctophilin-2 cleavage delays heart failure progression following myocardial infarction.Journal of molecular and cellular cardiology · 2024Article
- Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.Biomedicines · 2024Review
- Reduction of Filamin C Results in Altered Proteostasis, Cardiomyopathy, and Arrhythmias.Journal of the American Heart Association · 2024Article
- BAG3 localizes to mitochondria in cardiac fibroblasts and regulates mitophagy.American journal of physiology. Heart and circulatory physiology · 2024Article
- BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.Cardiovascular diabetology · 2024Article
- Biomarkers in Peripartum Cardiomyopathy-What We Know and What Is Still to Be Found.Biomolecules · 2024Review
- Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co-Occurrence of P63A and P380SJournal of the American Heart Association · 2023Article
- Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles.ACS materials Au · 2023Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure. Here, we found that cardiac-specific Bag3-KO and E455K-knockin mice developed DCM. Comparable phenotypes in the 2 mutants demonstrated that the E455K mutation resulted in loss of function. Further experiments revealed that the E455K mutation disrupted the interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a subset of proteins required for cardiomyocyte function was enriched in the insoluble fraction. Together, these observations suggest that interaction between BAG3 and HSP70 is essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide insight into heart failure caused by defects in BAG3 pathways and suggest that increasing BAG3 protein levels may be of therapeutic benefit in heart failure.
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