ArticleThe Journal of biological chemistry2012
Human heat shock protein 105/110 kDa (Hsp105/110) regulates biogenesis and quality control of misfolded cystic fibrosis transmembrane conductance regulator at multiple levels.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins.Nature communications · 2026Article
- Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.bioRxiv : the preprint server for biology · 2025Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Profiling the Hsp70 Chaperone Network in Heat-Induced Proteotoxic Stress Models of Human Neurons.Biology · 2023Article
- Role of BAG5 in Protein Quality Control: Double-Edged Sword?Frontiers in aging · 2022Review
- Review
- Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.International journal of molecular sciences · 2020Review
- HDAC inhibitors rescue multiple disease-causing CFTR variants.Human molecular genetics · 2019Article
- The Hsp70/J-protein machinery of the African trypanosome, Trypanosoma brucei.Cell stress & chaperones · 2019Article
- A Proteomic Variant Approach (ProVarA) for Personalized Medicine of Inherited and Somatic Disease.Journal of molecular biology · 2018Article
- Correcting the F508del-CFTR variant by modulating eukaryotic translation initiation factor 3-mediated translation initiation.The Journal of biological chemistry · 2018Article
- Substrate binding by the yeast Hsp110 nucleotide exchange factor and molecular chaperone Sse1 is not obligate for its biological activities.Molecular biology of the cell · 2017Article
- Cloning, expression of a truncated HSP110 protein that augments the activities of tumor antigen-specific cytotoxic and apoptosis via tHSP110-peptide complex vaccines.International journal of clinical and experimental pathology · 2017Article
- Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia.American journal of cancer research · 2017Article
- hERG quality control and the long QT syndrome.The Journal of physiology · 2016Review
- BAG2 structure, function and involvement in disease.Cellular & molecular biology letters · 2016Review
- Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications.Frontiers in immunology · 2016Review
- Hallmarks of therapeutic management of the cystic fibrosis functional landscape.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Review
- A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane.PLoS pathogens · 2015Article
- The nucleotide exchange factors of Hsp70 molecular chaperones.Frontiers in molecular biosciences · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein 105/110-kDa (Hsp105/110), a member of the Hsp70 super family of molecular chaperones, serves as a nucleotide exchange factor for Hsc70, independently prevents the aggregation of misfolded proteins, and functionally relates to Hsp90. We investigated the roles of human Hsp105α, the constitutively expressed isoform, in the biogenesis and quality control of the cystic fibrosis transmembrane conductance regulator (CFTR). In the endoplasmic reticulum (ER), Hsp105 facilitates CFTR quality control at an early stage in its biosynthesis but promotes CFTR post-translational folding. Deletion of Phe-508 (ΔF508), the most prevalent mutation causing cystic fibrosis, interferes with de novo folding of CFTR, impairing its export from the ER and accelerating its clearance in the ER and post-Golgi compartments. We show that Hsp105 preferentially associates with and stabilizes ΔF508 CFTR at both levels. Introduction of the Hsp105 substrate binding domain potently increases the steady state level of ΔF508 CFTR by reducing its early-stage degradation. This in turn dramatically enhances ΔF508 CFTR cell surface functional expression in cystic fibrosis airway epithelial cells. Although other Hsc70 nucleotide exchange factors such as HspBP1 and BAG-2 inhibit CFTR post-translational degradation in the ER through cochaperone CHIP, Hsp105 has a primary role promoting CFTR quality control at an earlier stage. The Hsp105-mediated multilevel regulation of ΔF508 CFTR folding and quality control provides new opportunities to understand how chaperone machinery regulates the homeostasis and functional expression of misfolded proteins in the cell. Future studies in this direction will inform therapeutics development for cystic fibrosis and other protein misfolding diseases.
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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.