ArticleMolecular biology of the cell2011
Role of Hsc70 binding cycle in CFTR folding and endoplasmic reticulum-associated degradation.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 44 citations in OpenAlex.
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Structures of the 26Science advances · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Native CFTR codon bias controls translation rate to balance off-pathway aggregation and channel function by conformational imprinting.Scientific reports · 2025Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.International journal of molecular sciences · 2023Review
- Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022Review
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021Review
- CFTR trafficking mutations disrupt cotranslational protein folding by targeting biosynthetic intermediates.Nature communications · 2020Article
- Review
- Selective Binding of HSC70 and its Co-Chaperones to Structural Hotspots on CFTR.Scientific reports · 2020Article
- Disposing of misfolded ER proteins: A troubled substrate's way out of the ER.Molecular and cellular endocrinology · 2020Review
- Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.International journal of molecular sciences · 2020Review
- Hsp70 and DNAJA2 limit CFTR levels through degradation.PloS one · 2019Article
- The evolving role of ubiquitin modification in endoplasmic reticulum-associated degradation.The Biochemical journal · 2017Review
- Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.The Journal of biological chemistry · 2017Article
- From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.Cellular and molecular life sciences : CMLS · 2017Review
- Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications.American journal of physiology. Lung cellular and molecular physiology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Hsp/c70 cytosolic chaperone system facilitates competing pathways of protein folding and degradation. Here we use a reconstituted cell-free system to investigate the mechanism and extent to which Hsc70 contributes to these co- and posttranslational decisions for the membrane protein cystic fibrosis transmembrane conductance regulator (CFTR). Hsc70 binding to CFTR was destabilized by the C-terminal domain of Bag-1 (CBag), which stimulates client release by accelerating ADP-ATP exchange. Addition of CBag during CFTR translation slightly increased susceptibility of the newly synthesized protein to degradation, consistent with a profolding function for Hsc70. In contrast, posttranslational destabilization of Hsc70 binding nearly completely blocked CFTR ubiquitination, dislocation from the endoplasmic reticulum, and proteasome-mediated cleavage. This effect required molar excess of CBag relative to Hsc70 and was completely reversed by the CBag-binding subdomain of Hsc70. These results demonstrate that the profolding role of Hsc70 during cotranslational CFTR folding is counterbalanced by a dominant and essential role in posttranslational targeting to the ubiquitin-proteasome system. Moreover, the degradative outcome of Hsc70 binding appears highly sensitive to the duration of its binding cycle, which is in turn governed by the integrated expression of regulatory cochaperones.
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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.