{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim Chiaw P"],"funding":["Cystic Fibrosis Canada","Canadian Institutes of Health Research","CIHR"],"pagination":["e0220984"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6692068"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(8)"],"pubmed_abstract":["Cystic Fibrosis is caused by mutations in the CFTR anion channel, many of which cause its misfolding and degradation. CFTR folding depends on the Hsc70 and Hsp70 chaperones and their co-chaperone DNAJA1, but Hsc70/Hsp70 is also involved in CFTR degradation. Here, we address how these opposing functions are balanced. DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by Hsc70/Hsp70 and the E3 ubiquitin ligase CHIP. Excess Hsp70 also promoted CFTR degradation, but this occurred through the lysosomal pathway and required CHIP but not complex formation with HOP and Hsp90. Notably, the Hsp70 inhibitor MKT077 enhanced levels of mature CFTR and the most common disease variant ΔF508-CFTR, by sl"],"journal":["PloS one"],"pubmed_title":["Hsp70 and DNAJA2 limit CFTR levels through degradation."],"pmcid":["PMC6692068"],"funding_grant_id":["MOP-133451","CFC 2634","MOP-130332","PJT-159666"],"pubmed_authors":["Young JC","Matthes E","Shrier A","Wong MJH","Robert R","Hantouche C","Hanrahan JW","Kim Chiaw P"],"additional_accession":[]},"is_claimable":false,"name":"Hsp70 and DNAJA2 limit CFTR levels through degradation.","description":"Cystic Fibrosis is caused by mutations in the CFTR anion channel, many of which cause its misfolding and degradation. CFTR folding depends on the Hsc70 and Hsp70 chaperones and their co-chaperone DNAJA1, but Hsc70/Hsp70 is also involved in CFTR degradation. Here, we address how these opposing functions are balanced. DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by Hsc70/Hsp70 and the E3 ubiquitin ligase CHIP. Excess Hsp70 also promoted CFTR degradation, but this occurred through the lysosomal pathway and required CHIP but not complex formation with HOP and Hsp90. Notably, the Hsp70 inhibitor MKT077 enhanced levels of mature CFTR and the most common disease variant ΔF508-CFTR, by sl","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019","modification":"2025-04-04T19:03:57.508Z","creation":"2019-09-04T07:07:35Z"},"accession":"S-EPMC6692068","cross_references":{"pubmed":["31408507"],"doi":["10.1371/journal.pone.0220984"]}}