ArticleThe Journal of biological chemistry2011
FKBP38 peptidylprolyl isomerase promotes the folding of cystic fibrosis transmembrane conductance regulator in the endoplasmic reticulum.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins.Nature communications · 2026Article
- Review
- HSP90 differentially stabilizes plant ABCB-type auxin transporters on the plasma membrane.Nature communications · 2025Article
- GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.Cancer biomarkers : section A of Disease markers · 2024Article
- Article
- Loss of Multiple ABCB Auxin Transporters Recapitulates the MajorFrontiers in plant science · 2022Article
- Regulation of ClC-2 Chloride Channel Proteostasis by Molecular Chaperones: Correction of Leukodystrophy-Associated Defect.International journal of molecular sciences · 2021Article
- Auxin-transporting ABC transporters are defined by a conserved D/E-P motif regulated by a prolylisomerase.The Journal of biological chemistry · 2020Article
- FKBP8 Enhances Protein Stability of the CLC-1 Chloride Channel at the Plasma Membrane.International journal of molecular sciences · 2018Article
- Article
- FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice.Journal of molecular and cellular cardiology · 2018Article
- Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.Scientific reports · 2016Article
- TWISTED DWARF1 Mediates the Action of Auxin Transport Inhibitors on Actin Cytoskeleton Dynamics.The Plant cell · 2016Article
- A novel Hsp70 inhibitor prevents cell intoxication with the actin ADP-ribosylating Clostridium perfringens iota toxin.Scientific reports · 2016Article
- Direct Interaction between Ras Homolog Enriched in Brain and FK506 Binding Protein 38 in Cashmere Goat Fetal Fibroblast Cells.Asian-Australasian journal of animal sciences · 2014Article
- The hop-like stress-induced protein 1 cochaperone is a novel cell-intrinsic restriction factor for mitochondrial tombusvirus replication.Journal of virology · 2014Article
- Mutations in intracellular loops 1 and 3 lead to misfolding of human P-glycoprotein (ABCB1) that can be rescued by cyclosporine A, which reduces its association with chaperone Hsp70.The Journal of biological chemistry · 2013Article
- Crucial role for phylogenetically conserved cytoplasmic loop 3 in ABCC4 protein expression.The Journal of biological chemistry · 2013Article
- Sequence and structure-specific elements of HERG mRNA determine channel synthesis and trafficking efficiency.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- FK506 binding protein 8 peptidylprolyl isomerase activity manages a late stage of cystic fibrosis transmembrane conductance regulator (CFTR) folding and stability.The Journal of biological chemistry · 2012Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
FK506-binding protein 38 (FKBP38), a membrane-anchored, tetratricopeptide repeat (TPR)-containing immunophilin, associates with nascent plasma membrane ion channels in the endoplasmic reticulum (ER). It promotes the maturation of the human ether-à-go-go-related gene (HERG) potassium channel and maintains the steady state level of the cystic fibrosis transmembrane conductance regulator (CFTR), but the underlying mechanisms remain unclear. Using a combination of steady state and pulse-chase analyses, we show that FKBP38 knockdown increases protein synthesis but inhibits the post-translational folding of CFTR, leading to reduced steady state levels of CFTR in the ER, decreased processing, and impaired cell surface functional expression in Calu-3 human airway epithelial cells. The membrane anchorage of FKBP38 is necessary for the inhibition of protein synthesis but not for CFTR post-translational folding. In contrast, the peptidylprolyl cis/trans isomerase active site is utilized to promote CFTR post-translational folding but is not important for regulation of protein synthesis. Uncoupling FKBP38 from Hsp90 by substituting a conserved lysine in the TPR domain modestly enhances CFTR maturation and further reduces its synthesis. Removing the N-terminal glutamate-rich domain (ERD) slightly enhances CFTR synthesis but reduces its maturation, suggesting that the ERD contributes to FKBP38 biological activities. Our data support a dual role for FKBP38 in regulating CFTR synthesis and post-translational folding. In contrast to earlier prediction but consistent with in vitro enzymological studies, FKBP38 peptidylprolyl cis/trans isomerase plays an important role in membrane protein biogenesis on the cytoplasmic side of the ER membrane, whose activity is negatively regulated by Hsp90 through the TPR domain.
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