ArticleJCI insight2018
HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- HSP70 Interactome-Mediated Proteolysis Targeting Chimera (HSP70-PROTAC) for Ferroptosis-Driven Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Going Further With Half as Much: It's in the BAG.JACC. Basic to translational science · 2023Article
- An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3.JACC. Basic to translational science · 2023Article
- Cardiac splicing as a diagnostic and therapeutic target.Nature reviews. Cardiology · 2023Review
- An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2023Review
- Virus-free transfection, transient expression, and purification of human cardiac myosin in mammalian muscle cells for biochemical and biophysical assays.Scientific reports · 2023Article
- Article
- Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice.Journal of the American Heart Association · 2022Article
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
- Translation of New and Emerging Therapies for Genetic Cardiomyopathies.JACC. Basic to translational science · 2022Review
- Inhibition of HSC70 alleviates hypertrophic cardiomyopathy pathology in human induced pluripotent stem cell-derived cardiomyocytes with a MYBPC3 mutation.Clinical and translational medicine · 2021Article
- Protein haploinsufficiency drivers identify MYBPC3 variants that cause hypertrophic cardiomyopathy.The Journal of biological chemistry · 2021Article
- Nanomechanical Phenotypes in Cardiac Myosin-Binding Protein C Mutants That Cause Hypertrophic Cardiomyopathy.ACS nano · 2021Article
- Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.G3 (Bethesda, Md.) · 2021Article
- Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy.Frontiers in cardiovascular medicine · 2021Review
- Article
- Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.Journal of molecular and cellular cardiology · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac myosin binding protein C (MYBPC3) is the most commonly mutated gene associated with hypertrophic cardiomyopathy (HCM). Haploinsufficiency of full-length MYBPC3 and disruption of proteostasis have both been proposed as central to HCM disease pathogenesis. Discriminating the relative contributions of these 2 mechanisms requires fundamental knowledge of how turnover of WT and mutant MYBPC3 proteins is regulated. We expressed several disease-causing mutations in MYBPC3 in primary neonatal rat ventricular cardiomyocytes. In contrast to WT MYBPC3, mutant proteins showed reduced expression and failed to localize to the sarcomere. In an unbiased coimmunoprecipitation/mass spectrometry screen, we identified HSP70-family chaperones as interactors of both WT and mutant MYBPC3. Heat shock cognate 70 kDa (HSC70) was the most abundant chaperone interactor. Knockdown of HSC70 significantly slowed degradation of both WT and mutant MYBPC3, while pharmacologic activation of HSC70 and HSP70 accelerated degradation. HSC70 was expressed in discrete striations in the sarcomere. Expression of mutant MYBPC3 did not affect HSC70 localization, nor did it induce a protein folding stress response or ubiquitin proteasome dysfunction. Together these data suggest that WT and mutant MYBPC3 proteins are clients for HSC70, and that the HSC70 chaperone system plays a major role in regulating MYBPC3 protein turnover.
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What OpenQuestion holds
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.