| http://purl.uniprot.org/citations/33094816 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33094816 | http://www.w3.org/2000/01/rdf-schema#comment | "Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL domains of USP19 and structural insights into their domain interactions. We found that the tandem CS domains fold back to interact with the C-terminal USP domain (USPD) intra-molecularly that leads to inhibition of the catalytic core of USP19, especially CS1 interacts with the embedded UbL domain and CS2 does with the CH2 catalytic core. Moreover, CS2 specifically interacts with the NBD domain of HSP90, which can activate the DUB enzyme. A mechanism of auto-inhibition of USP19 and activation by HSP90 is proposed, on which USP19 modulates the protein level of polyQ-expanded huntingtin in cells. This study provides structural and mechanistic insights into the modulation of protein level and aggregation by USP19 with the assistance of HSP90."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.org/dc/terms/identifier | "doi:10.1042/bcj20200536"xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "Hong J.Y."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "Xue W."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "Zhang S.X."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "Hu H.Y."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "Jiang L.L."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/author | "He W.T."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/pages | "4295-4312"xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/title | "Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation."xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://purl.uniprot.org/core/volume | "477"xsd:string |
| http://purl.uniprot.org/citations/33094816 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33094816 |
| http://purl.uniprot.org/citations/33094816 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33094816 |
| http://purl.uniprot.org/uniprot/#_O94966-mappedCitation-33094816 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33094816 |
| http://purl.uniprot.org/uniprot/O94966 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/33094816 |