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http://purl.uniprot.org/citations/30485852http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30485852http://www.w3.org/2000/01/rdf-schema#comment"

Background/aims

Cystic fibrosis (CF) is a lethal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR). ΔF508, the most common mutation, is a misfolded protein that is retained in the endoplasmic reticulum and degraded, precluding delivery to the cell surface [1].

Methods

Here we use a combination of western blotting, immunoprecipitation, and short circuit current techniques combined with confocal microscopy to address whether the SNARE attachment protein, STX8 plays a role in ΔF508's processing and movement out of the ER.

Results

Although the SNARE protein STX8 is thought to be functionally related and primarily localized to early endosomes, we show that silencing of STX8, particularly in the presence of the Vertex corrector molecule C18, rescues ΔF508-CFTR, allowing it to reach the cell surface and increasing CFTR-dependent chloride currents by approximately 2.5-fold over control values. STX8 silencing reduced the binding of quality control protein, Hsp 27, a protein that targets ΔF508-CFTR for sumoylation and subsequent degradation, to ΔF508-CFTR. STX8 silencing increased the levels of Hsp 60 a protein involving in early events in protein folding.

Conclusion

STX8 knockdown creates an environment favorable for mature ΔF508 to reach the cell surface. The data also suggest that when present at normal levels, STX8 functions as part of the cell's quality control mechanism."xsd:string
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http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/author"Guggino W.B."xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/author"Cebotaru L."xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/author"Boinot C."xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/author"Sabirzhanova I."xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/name"Cell Physiol Biochem"xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/pages"1489-1499"xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/title"Syntaxin 8 and the Endoplasmic Reticulum Processing of DeltaF508-CFTR."xsd:string
http://purl.uniprot.org/citations/30485852http://purl.uniprot.org/core/volume"51"xsd:string
http://purl.uniprot.org/citations/30485852http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30485852
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