| http://purl.uniprot.org/citations/20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20151404 | http://www.w3.org/2000/01/rdf-schema#comment | "Keratin (K) intermediate filament proteins form cytoskeletal scaffolds in epithelia, the disruption of which leads to a large number of human disorders. KRT5 or KRT14 mutations cause epidermolysis bullosa simplex (EBS). The considerable intra- and interfamilial variability in EBS suggests modifying loci, most of which are unknown. In many human disorders, chaperones and the ubiquitin-proteasome system have been found to modify disease severity, thereby providing novel therapy targets. Here, we demonstrate upregulation of stress-induced Hsp70 and Hsp90 in two EBS models, namely, in neonatal K5(-/-) mice and upon proteasome inhibition in cells that stably express the disease-causing mutation K14-p.Arg125Cys, both harboring keratin aggregates. Furthermore, proteasome inhibition caused nuclear translocation of pHSF-1 and an increase in K14-p.Arg125Cys-positive aggregates in cells. Overexpression of the chaperone-associated ubiquitin ligase CHIP/STUB1 strongly reduced keratin aggregates through increased degradation of mutant K14. Using CHIP-p.Met1_Ala142del (DeltaTPR-CHIP), we demonstrated the involvement of Hsc70 and Hsp70 in mutant keratin degradation. Our data uncover common principles between EBS and other protein misfolding disorders, revealing that aggregation-prone keratins are targeted by components of the chaperone machinery. Thus, modulation of the chaperone machinery using small molecules may represent a novel therapeutic strategy for dominant EBS, allowing reformation of an intact keratin cytoskeleton."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.21222"xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Woll S."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Hohfeld J."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Leube R.E."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Bruckner-Tuderman L."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Magin T.M."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Has C."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/author | "Loffek S."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/name | "Hum Mutat"xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/pages | "466-476"xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/title | "The ubiquitin ligase CHIP/STUB1 targets mutant keratins for degradation."xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://purl.uniprot.org/core/volume | "31"xsd:string |
| http://purl.uniprot.org/citations/20151404 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20151404 |
| http://purl.uniprot.org/citations/20151404 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20151404 |
| http://purl.uniprot.org/uniprot/#_B4E1T1-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_B4DL32-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_Q13092-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_P13647-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_Q922U2-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_P02533-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_Q32P04-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |
| http://purl.uniprot.org/uniprot/#_Q9CRS6-mappedCitation-20151404 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20151404 |