ArticleNature communications2018
Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 89 citations in OpenAlex.
- Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function.Circulation research · 2026Article
- Biogenesis of TNF-α-insights into proteostasis and inflammation.The FEBS journal · 2026Review
- Exploratory proteomic analysis of Megaconial congenital muscular dystrophy skeletal myoblasts suggests cytoskeletal and contractile alterations.BMC neurology · 2026Article
- Deletion of Murine Endothelial <italic>Bag3</italic> Alters the Cellular Proteome among Organs of Origin.Journal of vascular research · 2026Article
- Blockage of autophagy causes severe skeletal muscle disruption in a mouse model for myofibrillar myopathy 6.Nature communications · 2026Article
- AAV-Delivered RNAi Targeting Mutant LDB3 Prevents and Reverses Myofibrillar Myopathy through Mechanosignaling Restoration.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Neonatal propofol exposure impairs synaptic plasticity and cognition, associated with BAG3 upregulation and disrupted synaptic protein homeostasis.Frontiers in neuroscience · 2026Article
- Disease spectrum and long-term prognosis of patients with BAG3-associated neuromuscular diseases in Europe.Brain : a journal of neurology · 2025Article
- Small-Molecule Targeting MuRF1 Protects Against Denervation-Induced Diaphragmatic Dysfunction: Underlying Molecular Mechanisms.Journal of cachexia, sarcopenia and muscle · 2025Article
- TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins.Nature cell biology · 2025Article
- Review
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease.Science advances · 2025Article
- Identification of phosphatases that dephosphorylate the co-chaperone BAG3.Life science alliance · 2025Article
- Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.The Journal of clinical investigation · 2025Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- UNC-45 assisted myosin folding depends on a conserved FXNature communications · 2024Article
- BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.Cardiovascular diabetology · 2024Article
- BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1.Autophagy · 2024Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
Abstract
BAG3 is a multi-domain hub that connects two classes of chaperones, small heat shock proteins (sHSPs) via two isoleucine-proline-valine (IPV) motifs and Hsp70 via a BAG domain. Mutations in either the IPV or BAG domain of BAG3 cause a dominant form of myopathy, characterized by protein aggregation in both skeletal and cardiac muscle tissues. Surprisingly, for both disease mutants, impaired chaperone binding is not sufficient to explain disease phenotypes. Recombinant mutants are correctly folded, show unaffected Hsp70 binding but are impaired in stimulating Hsp70-dependent client processing. As a consequence, the mutant BAG3 proteins become the node for a dominant gain of function causing aggregation of itself, Hsp70, Hsp70 clients and tiered interactors within the BAG3 interactome. Importantly, genetic and pharmaceutical interference with Hsp70 binding completely reverses stress-induced protein aggregation for both BAG3 mutations. Thus, the gain of function effects of BAG3 mutants act as Achilles heel of the HSP70 machinery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.