ArticleMolecular biology of the cell2004
Distinct roles for the Hsp40 and Hsp90 molecular chaperones during cystic fibrosis transmembrane conductance regulator degradation in yeast.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 162 citations in OpenAlex.
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
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- Hsp90 and cochaperones have two genetically distinct roles in regulating eEF2 function.PLoS genetics · 2024Article
- Proteostasis in T cell aging.Seminars in immunology · 2023Review
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- An Integrated Approach Reveals DNA Damage and Proteotoxic Stress as Main Effects of Proton Radiation inInternational journal of molecular sciences · 2022Article
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- SLC26A9 is selected for endoplasmic reticulum associated degradation (ERAD) via Hsp70-dependent targeting of the soluble STAS domain.The Biochemical journal · 2021Article
- Functional and Stress Response Analysis of Heat Shock Proteins 40 and 90 of Giant River Prawn (Biomolecules · 2021Article
- Dosage sensitivity of JDPs, a valuable tool for understanding their function: a case study on Caj1 overexpression-mediated filamentous growth in budding yeast.Current genetics · 2021Review
- Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors.EMBO reports · 2021Article
- Small Hsps as Therapeutic Targets of Cystic Fibrosis Transmembrane Conductance Regulator Protein.International journal of molecular sciences · 2021Review
- Inner-nuclear-membrane-associated degradation employs Dfm1-independent retrotranslocation and alleviates misfolded transmembrane-protein toxicity.Molecular biology of the cell · 2021Article
- Direct involvement of Hsp70 ATP hydrolysis in Ubr1-dependent quality control.Molecular biology of the cell · 2020Article
- Ubiquitination of disease-causing CFTR variants in a microsome-based assay.Analytical biochemistry · 2020Article
- Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.International journal of molecular sciences · 2020Review
- Protein quality control in the secretory pathway.The Journal of cell biology · 2019Review
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Protein Topology Prediction Algorithms Systematically Investigated in the Yeast Saccharomyces cerevisiae.BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Article
- Targeting DNAJB9, a novel ER luminal co-chaperone, to rescue ΔF508-CFTR.Scientific reports · 2019Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Aberrant secreted proteins can be destroyed by ER-associated protein degradation (ERAD), and a prominent, medically relevant ERAD substrate is the cystic fibrosis transmembrane conductance regulator (CFTR). To better define the chaperone requirements during CFTR maturation, the protein was expressed in yeast. Because Hsp70 function impacts CFTR biogenesis in yeast and mammals, we first sought ER-associated Hsp40 cochaperones involved in CFTR maturation. Ydj1p and Hlj1p enhanced Hsp70 ATP hydrolysis but CFTR degradation was slowed only in yeast mutated for both YDJ1 and HLJ1, suggesting functional redundancy. In contrast, CFTR degradation was accelerated in an Hsp90 mutant strain, suggesting that Hsp90 preserves CFTR in a folded state, and consistent with this hypothesis, Hsp90 maintained the solubility of an aggregation-prone domain (NBD1) in CFTR. Soluble ERAD substrate degradation was unaffected in the Hsp90 or the Ydj1p/Hlj1p mutants, and surprisingly CFTR degradation was unaffected in yeast mutated for Hsp90 cochaperones. These results indicate that Hsp90, but not the Hsp90 complex, maintains CFTR structural integrity, whereas Ydj1p/Hlj1p catalyze CFTR degradation.
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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.