دورية أكاديمية
أعرض في EDS

Hsp70 and DNAJA2 limit CFTR levels through degradation.

التفاصيل البيبلوغرافية
العنوان: Hsp70 and DNAJA2 limit CFTR levels through degradation.
المؤلفون: Patrick Kim Chiaw, Christine Hantouche, Michael J H Wong, Elizabeth Matthes, Renaud Robert, John W Hanrahan, Alvin Shrier, Jason C Young
المصدر: PLoS ONE, Vol 14, Iss 8, p e0220984 (2019)
بيانات النشر: Public Library of Science (PLoS), 2019.
سنة النشر: 2019
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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 slowing turnover and allowing delayed maturation, respectively. MKT077 also boosted the channel activity of ΔF508-CFTR when combined with the corrector compound VX809. Thus, the Hsp70 system is the major determinant of CFTR degradation, and its modulation can partially relieve the misfolding phenotype.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0220984
URL الوصول: https://doaj.org/article/80281f7f22984ccf97aa287ac7cca643
رقم الأكسشن: edsdoj.80281f7f22984ccf97aa287ac7cca643
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0220984