Folding Biology of Cystic Fibrosis: A Consortium‐Based Approach to Disease

Balch, William E.; Braakman, Ineke; Brodsky, Jeff; Frizzell, Raymond; Guggino, William B.; Lukacs, Gergely L.; Penland, Christopher M.; Pollard, Harvey B.; Skach, William R.; Sorscher, Eric J.; Thomas, Philip

doi:10.1002/9780470572702.ch19

Protein Misfolding Diseases 2010

DOI: 10.1002/9780470572702.ch19

|View full text |Cite

Folding Biology of Cystic Fibrosis: A Consortium‐Based Approach to Disease

William E. Balch¹,

Ineke Braakman²,

Jeff Brodsky³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2011

Publication Types

Select...

Article1

Relationship

Self Cite1

Independent0

Authors

Journals

Cited by 1 publication

(2 citation statements)

References 172 publications

(206 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 This mutation results in a misfolded protein that is retained in the endoplasmic reticulum (ER), resulting in its degradation by the ubiquitin proteosomal system (UPS), such that little reaches the cell surface. 6–8 …”

mentioning

confidence: 99%

“…The disease is caused by defective trafficking and/or function of the CF transmembrane conductance regulator (CFTR) protein, a cAMP-activated channel that conducts chloride and bicarbonate ions across the apical plasma membrane, and controls trans-epithelial sodium ion transport. − About 90% of cases involve the deletion of phenylalanine-508 (ΔF508-CFTR) . This mutation results in a misfolded protein that is retained in the endoplasmic reticulum (ER), resulting in its degradation by the ubiquitin proteasomal system (UPS), such that little reaches the cell surface. − …”

mentioning

confidence: 99%

See 1 more Smart Citation

Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides That Restore Trafficking and Activity of ΔF508-CFTR

Hutt

Olsen

Vickers

et al. 2011

ACS Med. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a loss-of-function disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, a chloride ion channel that localizes to the apical plasma membrane of epithelial cells. The most common form of the disease results from the deletion of phenylalanine-508 (ΔF508), leading to the accumulation of CFTR in the endoplasmic reticulum with a concomitant loss of chloride flux. We discovered that cyclic tetrapeptides, such as 11, 14, and 15, are able to correct the trafficking defect and restore cell surface activity of ΔF508-CFTR. Although this class of cyclic tetrapeptides is known to contain inhibitors of certain histone deacetylase (HDAC) isoforms, their HDAC inhibitory potencies did not directly correlate with their ability to rescue ΔF508-CFTR. In full HDAC profiling, 15 strongly inhibited HDACs 1, 2, 3, 10 and 11, but not HDACs 4–9. Although 15 had less potent IC50 values than reference agent vorinostat (2) in HDAC profiling, it was markedly more potent than 2 in rescuing ΔF508-CFTR. We suggest that specific HDACs can have a differential influence on correcting ΔF508-CFTR, which may reflect both deacetylase and protein scaffolding actions.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides That Restore Trafficking and Activity of ΔF508-CFTR

Hutt

Olsen

Vickers

et al. 2011

ACS Med. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Folding Biology of Cystic Fibrosis: A Consortium‐Based Approach to Disease

Cited by 1 publication

References 172 publications

Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides That Restore Trafficking and Activity of ΔF508-CFTR

Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides That Restore Trafficking and Activity of ΔF508-CFTR

Contact Info

Product

Resources

About