Publication
BAG-1 stabilizes mutant F508del-CFTR in a Ubiquitin-Like-Domain-Dependent Manner
| dc.contributor.author | Mendes, Filipa | |
| dc.contributor.author | Farinha, Carlos M. | |
| dc.contributor.author | Felício, Verónica | |
| dc.contributor.author | Alves, Paula C. | |
| dc.contributor.author | Vieira, Isabel | |
| dc.contributor.author | Amaral, Paulo C. | |
| dc.date.accessioned | 2013-03-22T11:59:09Z | |
| dc.date.available | 2013-03-22T11:59:09Z | |
| dc.date.issued | 2012-10 | |
| dc.description.abstract | Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the dysfunctional Cl- channel in Cystic Fibrosis, undergoes complex biosynthesis at the endoplasmic reticulum involving several molecular chaperones including Hsp70 and many co-chaperones. Bcl-2-associated athanogenes (BAGs) constitute a protein family sharing an Hsc70-binding domain. BAG-1 possesses an ubiquitin-like domain (Ub-LD) responsible for proteasomal association and for promoting substrate release from Hsc70/Hsp70 in vitro by accelerating the chaperone ATP/ADP exchange rate. Methods: Herein, we studied the in vivo effect of BAG-1 on the turnover and processing of wild type (wt)- and F508del-CFTR, the most frequent mutation in CF patients. Results: Results show that BAG-1 associates with both wt- and F508del-CFTR (in higher yields with the latter) through its Ub-LD and independently of Hsc70. Moreover, the immature form of F508del-CFTR (but not of wt-CFTR) is stabilized by BAG-1 overexpression, albeit in a cell-type specific way, without detectable maturation. Data also show that BAG-1 and the proteasome inhibitor ALLN are not additive on stabilizing F508del-CFTR and this effect depends on BAG-1 Ub-LD. Moreover, under BAG-1 overexpression, a reduction in ubiquitinylated-CFTR occurs suggesting that BAG-1 competes with Ub. Conclusion: Overall, data are compatible with a mechanism in which BAG-1 stabilizes F508del-CFTR by direct binding, probably competing out ubiquitin to partially avoid its proteasomal degradation. | por |
| dc.identifier.citation | Cell Physiol Biochem. 2012;30(5):1120-33. doi: 10.1159/000343303. Epub 2012 Oct 5 | por |
| dc.identifier.issn | 1015-8987 | |
| dc.identifier.other | doi: 10.1159/000343303 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/1533 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Karger | por |
| dc.relation.publisherversion | http://www.karger.com/Article/Abstract/343303 | por |
| dc.subject | Fibrose Quística | por |
| dc.subject | CFTR | por |
| dc.subject | ERAD | por |
| dc.subject | BAG-1 | por |
| dc.subject | Hsp70 | por |
| dc.subject | Ubiquitina | por |
| dc.subject | Doenças Genéticas | por |
| dc.title | BAG-1 stabilizes mutant F508del-CFTR in a Ubiquitin-Like-Domain-Dependent Manner | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 1133 | por |
| oaire.citation.startPage | 1120 | por |
| oaire.citation.title | Cell Physiology and Biochemistry | por |
| oaire.citation.volume | 30(5) | por |
| rcaap.rights | embargoedAccess | por |
| rcaap.type | article | por |
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