Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

No abstract is available for this paper.

• Publication year

  2017

• Venue

  Journal of Clinical Investigation

• Publication date

  2017-07-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1172/JCI94310PMID 28737513PMCID PMC5531406
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins.

  2017influential reference
• Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation

  2017cited by this paper
• Bcl-2-associated athanogene 3 protects the heart from ischemia/reperfusion injury.

  2016cited by this paper
• Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure

  2016cited by this paper
• IP3 receptors regulate vascular smooth muscle contractility and hypertension.

  2016cited by this paper
• Adipocyte-specific loss of PPARγ attenuates cardiac hypertrophy.

  2016cited by this paper
• Non-canonical Interactions between Heat Shock Cognate Protein 70 (Hsc70) and Bcl2-associated Anthanogene (BAG) Co-Chaperones Are Important for Client Release*

  2016cited by this paper
• Probing chromatin landscape reveals roles of endocardial TBX20 in septation.

  2016cited by this paper
• Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

  2016cited by this paper
• Proteotoxicity and cardiac dysfunction.

  2015cited by this paper
• Activation of PPAR‐δ induces microRNA‐100 and decreases the uptake of very low‐density lipoprotein in endothelial cells

  2015cited by this paper
• Normalization of Naxos plakoglobin levels restores cardiac function in mice.

  2015cited by this paper
• A first line of stress defense: small heat shock proteins and their function in protein homeostasis.

  2015cited by this paper
• Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome

  2014cited by this paper
• Decreased Levels of BAG3 in a Family With a Rare Variant and in Idiopathic Dilated Cardiomyopathy

  2014influential reference
• Nonsense mutations in BAG3 are associated with early-onset dilated cardiomyopathy in French Canadians.

  2014cited by this paper
• Activation of NADPH Oxidase 4 in the Endoplasmic Reticulum Promotes Cardiomyocyte Autophagy and Survival During Energy Stress Through the Protein Kinase RNA-Activated-Like Endoplasmic Reticulum Kinase/Eukaryotic Initiation Factor 2&agr;/Activating Transcription Factor 4 Pathway

  2013cited by this paper
• Binding of Human Nucleotide Exchange Factors to Heat Shock Protein 70 (Hsp70) Generates Functionally Distinct Complexes in Vitro*

  2013cited by this paper
• Proteotoxicity and cardiac dysfunction--Alzheimer's disease of the heart?

  2013cited by this paper
• The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways.

  2012cited by this paper
• Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease.

  2012cited by this paper
• Misfolded protein aggregates: mechanisms, structures and potential for disease transmission.

  2011cited by this paper
• Dilated cardiomyopathy‐associated BAG3 mutations impair Z‐disc assembly and enhance sensitivity to apoptosis in cardiomyocytes

  2011cited by this paper
• BAG3: a multifaceted protein that regulates major cell pathways

  2011cited by this paper
• Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.

  2011cited by this paper
• HSPB7 is the most potent polyQ aggregation suppressor within the HSPB family of molecular chaperones.

  2010cited by this paper
• Heat Shock Proteins: Cell Protection through Protein Triage

  2010cited by this paper
• Methods in mammalian autophagy research.

  2010cited by this paper
• Accurate Quantification of More Than 4000 Mouse Tissue Proteins Reveals Minimal Proteome Changes During Aging*

  2010cited by this paper
• Screening of fusion partners for high yield expression and purification of bioactive viscotoxins.

  2009cited by this paper
• The role of molecular chaperones in human misfolding diseases

  2009cited by this paper
• Identification of the key structural motifs involved in HspB8/HspB6-Bag3 interaction.

  2009cited by this paper
• Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3

  2009cited by this paper
• Protein misfolding and neurodegeneration.

  2008cited by this paper
• Mutation in BAG3 causes severe dominant childhood muscular dystrophy

  2008cited by this paper
• Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus.

  2008cited by this paper
• HspB8 Chaperone Activity toward Poly(Q)-containing Proteins Depends on Its Association with Bag3, a Stimulator of Macroautophagy*

  2008cited by this paper
• Regulation of cardiac hypertrophy by intracellular signalling pathways

  2006cited by this paper
• Heart failure and protein quality control.

  2006cited by this paper
• BAG3 deficiency results in fulminant myopathy and early lethality.

  2006cited by this paper
• Dilated cardiomyopathy resulting from high-level myocardial expression of Cre-recombinase.

  2006cited by this paper
• p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death

  2005influential reference
• p 62 / SQSTM 1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death

  2005cited by this paper
• The Identity of Proteins Associated with a Small Heat Shock Protein during Heat Stress in Vivo Indicates That These Chaperones Protect a Wide Range of Cellular Functions*

  2004cited by this paper
• Pathways of chaperone-mediated protein folding in the cytosol

  2004cited by this paper
• Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis.

  2004cited by this paper
• Hyperubiquitination of proteins in dilated cardiomyopathy

  2003cited by this paper
• Cytoscape: a software environment for integrated models of biomolecular interaction networks.

  2003cited by this paper
• In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker.

  2003cited by this paper
• Myocytes Die by Multiple Mechanisms in Failing Human Hearts

  2003cited by this paper
• What's in the 'BAG'?--A functional domain analysis of the BAG-family proteins.

  2002cited by this paper
• p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases.

  2002cited by this paper
• Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain.

  2002cited by this paper
• Toxic Proteins in Neurodegenerative Disease

  2002cited by this paper
• Folding of newly translated proteins in vivo: the role of molecular chaperones.

  2001cited by this paper
• Molecular chaperone targeting and regulation by BAG family proteins

  2001cited by this paper
• Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium.

  2000cited by this paper
• Aggresomes, inclusion bodies and protein aggregation.

  2000cited by this paper
• High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP

  2000cited by this paper
• An Evolutionarily Conserved Family of Hsp70/Hsc70 Molecular Chaperone Regulators*

  1999cited by this paper
• Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart.

  1999cited by this paper
• Aggresomes: A Cellular Response to Misfolded Proteins

  1998cited by this paper
• Protein aggregation: folding aggregates, inclusion bodies and amyloid.

  1998cited by this paper
• MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure.

  1997cited by this paper
• Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells.

  1991cited by this paper
• Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy

  1991cited by this paper
• Successive internal resorption.

  1990cited by this paper
• A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy

  year unknowncited by this paper

• Atorvastatin Protects Against Deleterious Carfilzomib-Induced Transcriptional Changes in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

  2026cites this paper
• A combined genomic arrhythmia propensity score delineates cumulative risk

  2025cites this paper
• Unraveling the Role of BAG3 in Hepatic Fibrosis: Genetic and Biomarker Insights in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

  2025cites this paper
• HSP22 Alleviates Lung Ischemia–Reperfusion Injury Following Pulmonary Embolism by Suppressing Inflammation, Oxidative Stress, and Apoptosis Through HIF‐1α/NOX4 Pathway

  2025cites this paper
• A patient-specific engineered tissue model of BAG3-mediated cardiomyopathy

  2025influential citation
• An mTOR‐Tfeb‐Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging

  2025cites this paper
• Nonstructural Roles of Junctophilin-2 in the Heart

  2025cites this paper
• Disrupted Sarcomere Reorganization of Cardiomyopathy-Prone Human iPSC-Derived Cardiomyocytes on a Dynamic Mechanical Substrate

  2025cites this paper
• Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer’s disease

  2025cites this paper
• Cardiomyocyte-specific activation of the sarcomere-localized Dnajb6b chaperone causes cardiomyopathy and heart failure through upregulated sarcoplasmic reticulum stress.

  2025cites this paper
• C-terminal extension of HSPB6 in a family with myopathy and cataract.

  2025cites this paper
• Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy

  2025cites this paper
• Cardiogenic Shock in a Young South Asian Male With Cardiomyopathy due to a Pathogenic Variant of BAG3 Gene

  2025cites this paper
• The BAG3-HSP70-CHIP axis controls the degradation of TGFBR2 in cardiac fibroblasts.

  2025cites this paper
• Biomarkers in Peripartum Cardiomyopathy—What We Know and What Is Still to Be Found

  2024cites this paper
• BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling

  2024cites this paper
• Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3.

  2024cites this paper
• Universal Adapter Protein Bag3 and Small Heat Shock Proteins

  2024cites this paper
• The essential role of MED27 in stabilizing the mediator complex for cardiac development and function.

  2024cites this paper
• The role of heat shock protein B8 in neuronal protection against oxidative stress and mitochondrial dysfunction: A literature review.

  2024cites this paper
• Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review

  2024cites this paper
• Targeting Calpain-2-mediated Junctophilin-2 cleavage delays heart failure progression following myocardial infarction.

  2024cites this paper
• Inhibition of autophagy prevents cardiac dysfunction at early stages of cardiomyopathy in Bag3-deficient hearts.

  2024cites this paper
• Reduction of Filamin C Results in Altered Proteostasis, Cardiomyopathy, and Arrhythmias

  2024cites this paper
• BAG3 localizes to mitochondria in cardiac fibroblasts and regulates mitophagy.

  2024cites this paper
• Shifting Paradigm from Gene Expressions to Pathways Reveals Physiological Mechanisms in Blood Pressure Control in Causation

  2023cites this paper
• Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity

  2023cites this paper
• Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co‐Occurrence of P63A and P380S BAG3 Variants

  2023influential citation
• Dilated cardiomyopathy: causes, mechanisms, and current and future treatment approaches.

  2023cites this paper
• Comprehensive review on gene mutations contributing to dilated cardiomyopathy

  2023cites this paper
• Going Further With Half as Much

  2023cites this paper
• Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles

  2023cites this paper
• Interaction of Filamin C With Actin Is Essential for Cardiac Development and Function

  2023cites this paper
• AZD7762 induces CRBN dependent BAG3 degradation through ubiquitin-proteasome pathway

  2023cites this paper
• BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis

  2023cites this paper
• Desmin mutations impact the autophagy flux in C2C12 cell in mutation-specific manner

  2023cites this paper
• Skeletal Muscle-Specific Bis Depletion Leads to Muscle Dysfunction and Early Death Accompanied by Impairment in Protein Quality Control

  2023influential citation
• Bag3 Regulates Mitochondrial Function and the Inflammasome Through Canonical and Noncanonical Pathways in the Heart

  2023cites this paper
• Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend on aggrephagy to maintain protein homeostasis.

  2023cites this paper
• Transcriptome studies of inherited dilated cardiomyopathies

  2023cites this paper
• The chaperone-assisted selective autophagy complex dynamics and dysfunctions

  2023cites this paper
• An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3

  2023cites this paper
• Autophagy in striated muscle diseases

  2022cites this paper
• The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases

  2022cites this paper
• GrpE is involved in mitochondrial function and is an effective target for RNAi‐mediated pest and arbovirus control

  2022cites this paper
• Liquid–Liquid Phase Separation in Cardiovascular Diseases

  2022cites this paper
• Fully Automated Mouse Echocardiography Analysis Using Deep Convolutional Neural Networks.

  2022cites this paper
• Phenotypic screening with deep learning identifies HDAC6 inhibitors as cardioprotective in a BAG3 mouse model of dilated cardiomyopathy

  2022cites this paper
• Hepatocyte-specific deletion of Bis causes senescence in the liver without deteriorating hepatic function.

  2022cites this paper
• Zebrafish Models of Cardiac Disease: From Fortuitous Mutants to Precision Medicine

  2022cites this paper
• Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy

  2022cites this paper
• Genetics of BAG3: A Paradigm for Developing Precision Therapies for Dilated Cardiomyopathies

  2022cites this paper
• Hsp22 Deficiency Induces Age-Dependent Cardiac Dilation and Dysfunction by Impairing Autophagy, Metabolism, and Oxidative Response

  2021influential citation
• Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

  2021cites this paper
• An Adult Mouse Model of Dilated Cardiomyopathy Caused by Inducible Cardiac-Specific Bis Deletion

  2021influential citation
• Different roles of BAG3 in cardiac physiological hypertrophy and pathological remodeling.

  2021cites this paper
• Functional analysis of a gene-edited mouse model to gain insights into the disease mechanisms of a titin missense variant

  2021cites this paper
• Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure

  2021cites this paper
• The role of BAG3 in health and disease: A “Magic BAG of Tricks”

  2021cites this paper
• BAG3 Expression and Sarcomere Localization in the Human Heart are Linked to HSF-1 and are Differentially Affected by Sex and Disease.

  2021cites this paper
• HSC70-JNK-BAG3 complex is critical for cardiomyocyte protection of BAG3 through its PXXP and BAG structural domains.

  2021cites this paper
• Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy

  2021cites this paper
• Cardiolipin Remodeling Defects Impair Mitochondrial Architecture and Function in a Murine Model of Barth Syndrome Cardiomyopathy

  2021cites this paper
• Maintaining proteostasis under mechanical stress

  2021cites this paper
• Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease.

  2021influential citation
• Pharmacological inhibition of BAG3‐HSP70 with the proposed cancer therapeutic JG‐98 is toxic for cardiomyocytes

  2021influential citation
• Mediator complex proximal Tail subunit MED30 is critical for Mediator core stability and cardiomyocyte transcriptional network

  2021cites this paper
• Functional analysis of a common BAG3 allele associated with protection from heart failure

  2021cites this paper
• Depletion of m6A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin

  2021cites this paper
• With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

  2021cites this paper
• Understanding the Molecular Basis of Cardiomyopathy.

  2021cites this paper
• Translation of New and Emerging Therapies for Genetic Cardiomyopathies

  2021cites this paper
• Regulation of neuronal autophagy and the implications in neurodegenerative diseases.

  2021cites this paper
• Detection of sieric BAG3 in patients affected by cardiovascular diseases: State of art and perspectives

  2021cites this paper
• Heat Shock Protein 22 in Physiological and Pathological Hearts: Small Molecule, Large Potentials

  2021cites this paper
• Changes in microRNA Expression Profiles in Diabetic Cardiomyopathy Rats Following H3 Relaxin Treatment

  2021cites this paper
• Genetic Cardiomyopathies

  2020cites this paper
• Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases.

  2020cites this paper
• Dilated Cardiomyopathy

  2020cites this paper
• BAG3 Proteomic Signature under Proteostasis Stress

  2020cites this paper
• Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

  2020cites this paper
• Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency

  2020influential citation
• Cardiomyocyte contractile impairment in heart failure results from reduced BAG3-mediated sarcomeric protein turnover

  2020cites this paper
• O-GlcNAcylation Is Essential for Autophagy in Cardiomyocytes

  2020cites this paper
• Homozygous G650del nexilin variant causes cardiomyopathy in mice

  2020cites this paper
• Nexilin Is Necessary for Maintaining the Transverse-Axial Tubular System in Adult Cardiomyocytes

  2020cites this paper
• Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

  2020cites this paper
• The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unreponsive to standard heart failure therapy

  2020cites this paper
• Identification of miRNA–mRNA–TFs Regulatory Network and Crucial Pathways Involved in Tetralogy of Fallot

  2020cites this paper
• Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis

  2020cites this paper
• BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes

  2020cites this paper
• Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction

  2020cites this paper
• Atypical ALPK2 kinase is not essential for cardiac development and function.

  2020cites this paper
• The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy

  2020cites this paper
• BAG3-dependent autophagy maintains sarcomere function in cardiomyocytes

  2020cites this paper
• Metformin rescues muscle function in BAG3 myofibrillar myopathy models

  2019cites this paper
• BAG3 Pro209 mutants associated with myopathy and neuropathy sequester chaperones of the CASA-complex in aggresomes

  2019cites this paper
• Investigation of a dilated cardiomyopathy-associated variant in BAG3 using genome-edited iPSC-derived cardiomyocytes.

  2019cites this paper
• Heart Failure in the Era of Precision Medicine: A Scientific Statement From the American Heart Association.

  2019cites this paper
• Haploinsufficiency of mechanistic target of rapamycin ameliorates bag3 cardiomyopathy in adult zebrafish

  2019influential citation