| http://purl.uniprot.org/citations/23990462 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23990462 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23990462 | http://www.w3.org/2000/01/rdf-schema#comment | "The C terminus of Hsp70 interacting protein (CHIP) E3 ligase functions as a key regulator of protein quality control by binding the C-terminal (M/I)EEVD peptide motif of Hsp/c70(90) with its N-terminal tetratricopeptide repeat (TPR) domain and facilitating polyubiquitination of misfolded client proteins via its C-terminal catalytic U-box. Using CFTR as a model client, we recently showed that the duration of the Hsc70-client binding cycle is a primary determinant of stability. However, molecular features that control CHIP recruitment to Hsp/c70, and hence the fate of the Hsp/c70 client, remain unknown. To understand how CHIP recognizes Hsp/c70, we utilized a dominant negative mutant in which loss of a conserved proline in the U-box domain (P269A) eliminates E3 ligase activity. In a cell-free reconstituted ER-associated degradation system, P269A CHIP inhibited Hsc70-dependent CFTR ubiquitination and degradation in a dose-dependent manner. Optimal inhibition required both the TPR and the U-box, indicating cooperativity between the two domains. Neither the wild type nor the P269A mutant changed the extent of Hsc70 association with CFTR nor the dissociation rate of the Hsc70-CFTR complex. However, the U-box mutation stimulated CHIP binding to Hsc70 while promoting CHIP oligomerization. CHIP binding to Hsc70 binding was also stimulated by the presence of an Hsc70 client with a preference for the ADP-bound state. Thus, the Hsp/c70 (M/I)EEVD motif is not a simple anchor for the TPR domain. Rather CHIP recruitment involves reciprocal allosteric interactions between its TPR and U-box domains and the substrate-binding and C-terminal domains of Hsp/c70."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.479345"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.479345"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Matsumura Y."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Matsumura Y."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Sakai J."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Sakai J."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Skach W.R."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/author | "Skach W.R."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/pages | "31069-31079"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/pages | "31069-31079"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/title | "Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/title | "Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase."xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/volume | "288"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://purl.uniprot.org/core/volume | "288"xsd:string |
| http://purl.uniprot.org/citations/23990462 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23990462 |
| http://purl.uniprot.org/citations/23990462 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23990462 |
| http://purl.uniprot.org/citations/23990462 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23990462 |
| http://purl.uniprot.org/citations/23990462 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23990462 |