ArticleThe Journal of clinical investigation2020
Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.EMBO reports · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis.Nature communications · 2026Article
- Molecular genetics of J-domain protein-related chaperonopathies in skeletal muscle.Journal of human genetics · 2025Review
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- Genotype‒phenotype correlation in recessive DNAJB4 myopathy.Acta neuropathologica communications · 2024Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model.Human molecular genetics · 2024Article
- Tertiary structure and conformational dynamics of the anti-amyloidogenic chaperone DNAJB6b at atomistic resolution.Nature communications · 2024Article
- Mrj is a chaperone of the Hsp40 family that regulates Orb2 oligomerization and long-term memory in Drosophila.PLoS biology · 2024Article
- DNAJB6 mutants display toxic gain of function through unregulated interaction with Hsp70 chaperones.Nature communications · 2023Article
- Extension of the DNAJB2a isoform in a dominant neuromyopathy family.Human molecular genetics · 2023Article
- DNAJB6 isoform specific knockdown: Therapeutic potential for limb girdle muscular dystrophy D1.Molecular therapy. Nucleic acids · 2023Article
- LGMDD1 natural history and phenotypic spectrum: Implications for clinical trials.Annals of clinical and translational neurology · 2023Observational
- Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications.International journal of molecular sciences · 2022Review
- The roles of HSP40/DNAJ protein family in neurodegenerative diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Disease-associated mutations within the yeast DNAJB6 homolog Sis1 slow conformer-specific substrate processing and can be corrected by the modulation of nucleotide exchange factors.Nature communications · 2022Article
- Review
- A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy.Acta neuropathologica communications · 2021Article
- Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome.Biomolecules · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Dominant mutations in the HSP70 cochaperone DNAJB6 cause a late-onset muscle disease termed limb-girdle muscular dystrophy type D1 (LGMDD1), which is characterized by protein aggregation and vacuolar myopathology. Disease mutations reside within the G/F domain of DNAJB6, but the molecular mechanisms underlying dysfunction are not well understood. Using yeast, cell culture, and mouse models of LGMDD1, we found that the toxicity associated with disease-associated DNAJB6 required its interaction with HSP70 and that abrogating this interaction genetically or with small molecules was protective. In skeletal muscle, DNAJB6 localizes to the Z-disc with HSP70. Whereas HSP70 normally diffused rapidly between the Z-disc and sarcoplasm, the rate of diffusion of HSP70 in LGMDD1 mouse muscle was diminished, probably because it had an unusual affinity for the Z-disc and mutant DNAJB6. Treating LGMDD1 mice with a small-molecule inhibitor of the DNAJ-HSP70 complex remobilized HSP70, improved strength, and corrected myopathology. These data support a model in which LGMDD1 mutations in DNAJB6 are a gain-of-function disease that is, counterintuitively, mediated via HSP70 binding. Thus, therapeutic approaches targeting HSP70-DNAJB6 may be effective in treating this inherited muscular dystrophy.
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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.