The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Misfolding diverts CFTR from recycling to degradation
Open accessAbstract
To investigate the degradation mechanism of misfolded membrane proteins from the cell surface, we used mutant cystic fibrosis transmembrane conductance regulators (CFTRs) exhibiting conformational defects in post-Golgi compartments. Here, we show that the folding state of CFTR determines the post-endocytic trafficking of the channel. Although native CFTR recycled from early endosomes back to the cell surface, misfolding prevented recycling and facilitated lysosomal targeting by promoting the ubiquitination of the channel. Rescuing the folding defect or down-regulating the E1 ubiquitin (Ub)-activating enzyme stabilized the mutant CFTR without interfering with its internalization. These observations with the preferential association of mutant CFTRs with Hrs, STAM-2, TSG101, hVps25, and hVps32, components of the Ub-dependent endosomal sorting machinery, establish a functional link between Ub modification and lysosomal degradation of misfolded CFTR from the cell surface. Our data provide evidence for a novel cellular mechanism of CF pathogenesis and suggest a paradigm for the quality control of plasma membrane proteins involving the coordinated function of ubiquitination and the Ub-dependent endosomal sorting machinery.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,184
Quality control in the endoplasmic reticulum
Ellgaard, L., & Helenius, A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1052 · Cited by 2,126
Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes
Bonifacino, J. S., & Traub, L. M. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161800 · Cited by 2,040
ENDOCYTOSIS AND MOLECULAR SORTING
Mellman, I. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.575 · Cited by 1,533
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,482
Mukherjee, S., Ghosh, R. N., & Maxfield, F. R. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.3.759 · Cited by 1,294
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive
Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., & Welsh, M. J. (1992) · Nature · doi:10.1038/358761a0 · Cited by 1,234
Receptor downregulation and multivesicular-body sorting
Katzmann, D. J., Odorizzi, G., & Emr, S. D. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm973 · Cited by 1,201
Setting the Standards: Quality Control in the Secretory Pathway
Ellgaard, L., Molinari, M., & Helenius, A. (1999) · Science · doi:10.1126/science.286.5446.1882 · Cited by 1,192
Regulation of Membrane Protein Transport by Ubiquitin and Ubiquitin-Binding Proteins
Hicke, L., & Dunn, R. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.110701.154617 · Cited by 1,106
Cited by
CFTR Function and Prospects for Therapy
Riordan, J. R. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142532 · Cited by 610
Multivesicular Body Morphogenesis
Hanson, P. I., & Cashikar, A. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154152 · Cited by 584
Younger, J. M., Chen, L., Ren, H.-Y., Rosser, M. F. N., Turnbull, E. L., Fan, C.-Y., Patterson, C., & Cyr, D. M. (2006) · Cell · doi:10.1016/j.cell.2006.06.041 · Cited by 440
Peripheral Protein Quality Control Removes Unfolded CFTR from the Plasma Membrane
Okiyoneda, T., Barrière, H., Bagdány, M., Rabeh, W. M., Du, K., Höhfeld, J., Young, J. C., & Lukacs, G. L. (2010) · Science · doi:10.1126/science.1191542 · Cited by 408
Self-citationCFTR: folding, misfolding and correcting the ΔF508 conformational defect
Lukacs, G. L., & Verkman, A. S. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.10.003 · Cited by 375
Self-citation
Metadata
- Authors
- Sharma, M., Pampinella, F., Nemes, C., Benharouga, M., So, J., Du, K., Bache, K. G., Papsin, B., Zerangue, N., Stenmark, H., & Lukacs, G. L.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-03-08
- Volume
- 164
- Issue
- 6
- Pages
- 923-933
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2107156397
- Cited by
- 329
- References
- 58
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Misfolding diverts CFTR from recycling to degradation. https://app.cochat.ai/papers/10.1083/jcb.200312018
- The paper
- Sharma, M., Pampinella, F., Nemes, C., Benharouga, M., So, J., Du, K., Bache, K. G., Papsin, B., Zerangue, N., Stenmark, H., & Lukacs, G. L. (2004). Misfolding diverts CFTR from recycling to degradation. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200312018
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
