ArticleMolecular biology of the cell2021
DNAJB12 and Hsp70 triage arrested intermediates of N1303K-CFTR for endoplasmic reticulum-associated autophagy.
Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Inhibition of the QPCT-PDIA4 axis rescues ΔF508 and N1303K CFTR in cystic fibrosis.Nature communications · 2026Article
- Unveiling DNAJB12 and DNAJB14 as crucial chaperones in hepatitis B and D virus particle morphogenesis.iScience · 2026Article
- Potential Risk Factors and Therapeutic Targets for Dilated Cardiomyopathy Identified Through Mendelian Randomization Analysis.Journal of the American Heart Association · 2026Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Proteostasis Landscapes of Cystic Fibrosis Variants Reveals Drug Response Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- Beyond Trikafta: new models to assess tissue dependent rescue of N1303K-CFTR.Frontiers in pharmacology · 2025Article
- BioID-Based Proximity Mapping of Transmembrane Proteins in Human Airway Cell Models.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Novel functions of the ER-located Hsp40s DNAJB12 and DNAJB14 on proteins at the outer mitochondrial membrane under stress mediated by CCCP.Molecular and cellular biochemistry · 2024Article
- Time-resolved interactome profiling deconvolutes secretory protein quality control dynamics.Molecular systems biology · 2024Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- J-domain proteins: From molecular mechanisms to diseases.Cell stress & chaperones · 2024Article
- Cystic fibrosis airway inflammation enables elexacaftor/tezacaftor/ivacaftor-mediated rescue of N1303KERJ open research · 2024Article
- Identification of novel biomarkers of ferroptosis involved in keloid based on bioinformatics analysis.International wound journal · 2024Article
- The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.Scientific reports · 2023Article
- Autophagy of the ER: the secretome finds the lysosome.The FEBS journal · 2023Review
- TOLLIP acts as a cargo adaptor to promote lysosomal degradation of aberrant ER membrane proteins.The EMBO journal · 2023Article
- Transmembrane Helices 7 and 8 Confer Aggregation Sensitivity to the Cystic Fibrosis Transmembrane Conductance Regulator.International journal of molecular sciences · 2023Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy.The Journal of cell biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The transmembrane Hsp40 DNAJB12 and cytosolic Hsp70 cooperate on the endoplasmic reticulum's (ER) cytoplasmic face to facilitate the triage of nascent polytopic membrane proteins for folding versus degradation. N1303K is a common mutation that causes misfolding of the ion channel CFTR, but unlike F508del-CFTR, biogenic and functional defects in N1303K-CFTR are resistant to correction by folding modulators. N1303K is reported to arrest CFTR folding at a late stage after partial assembly of its N-terminal domains. N1303K-CFTR intermediates are clients of JB12-Hsp70 complexes, maintained in a detergent-soluble state, and have a relatively long 3-h half-life. ER-associated degradation (ERAD)-resistant pools of N1303K-CFTR are concentrated in ER tubules that associate with autophagy initiation sites containing WIPI1, FlP200, and LC3. Destabilization of N1303K-CFTR or depletion of JB12 prevents entry of N1303K-CFTR into the membranes of ER-connected phagophores and traffic to autolysosomes. In contrast, the stabilization of intermediates with the modulator VX-809 promotes the association of N1303K-CFTR with autophagy initiation machinery. N1303K-CFTR is excluded from the ER-exit sites, and its passage from the ER to autolysosomes does not require ER-phagy receptors. DNAJB12 operates in biosynthetically active ER microdomains to triage membrane protein intermediates in a conformation-specific manner for secretion versus degradation via ERAD or selective-ER-associated autophagy.
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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.