| http://purl.uniprot.org/citations/33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33381997 | http://www.w3.org/2000/01/rdf-schema#comment | "Mineralocorticoid and androgen receptor antagonist, spironolactone, was recently identified as an inhibitor of nucleotide excision repair (NER), acting via induction of proteolysis of TFIIH component Xeroderma Pigmentosum B protein (XPB). This activity provides a strong rationale for repurposing spironolactone for cancer therapy. Here, we report that the spironolactone-induced XPB proteolysis is mediated through ubiquitin-selective segregase, valosin-containing protein (VCP)/p97. We show that spironolactone induces a dose- and time-dependent degradation of XPB but not XPD, and that the XPB degradation is blocked by VCP/p97 inhibitors DBeQ, NMS-873, and neddylation inhibitor MLN4924. Moreover, the cellular treatment by VCP/p97 inhibitors leads to the accumulation of ubiquitin conjugates of XPB but not XPD. VCP/p97 knockdown by inducible shRNA does not affect XPB level but compromises the spironolactone-induced XPB degradation. Also, VCP/p97 interacts with XPB upon treatment of spironolactone and proteasome inhibitor MG132, while the VCP/p97 adaptor UBXD7 binds XPB and its ubiquitin conjugates. Additionally, ATP analog-mediated inhibition of Cdk7 significantly decelerates spironolactone-induced XPB degradation. Likewise, engaging TFIIH to NER by UV irradiation slows down spironolactone-induced XPB degradation. These results indicate that the spironolactone-induced XPB proteolysis requires VCP/p97 function and that XPB within holo-TFIIH rather than core-TFIIH is more vulnerable to spironolactone-induced proteolysis. Abbreviations NER: nucleotide excision repair; TFIIH: transcription factor II H; CAK: Cdk-activating kinase (CAK) complex; XPB: Xeroderma Pigmentosum type B; VCP/p97: valosin-containing protein/p97; Cdk7: cyclin-dependent kinase 7; NAE: NEDD8-activating enzyme; IP: immunoprecipitation."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.org/dc/terms/identifier | "doi:10.1080/15384101.2020.1860559"xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Li P."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Zhu Q."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Chauhan A.K."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Wani A.A."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/author | "Wani G."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/name | "Cell Cycle"xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/pages | "81-95"xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/title | "Spironolactone-induced XPB degradation requires TFIIH integrity and ubiquitin-selective segregase VCP/p97."xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://purl.uniprot.org/core/volume | "20"xsd:string |
| http://purl.uniprot.org/citations/33381997 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33381997 |
| http://purl.uniprot.org/citations/33381997 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33381997 |
| http://purl.uniprot.org/uniprot/#_A8K359-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_B3KRG2-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_B4DTK4-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_B3KTH1-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_Q0IIN5-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_P55072-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_P19447-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_Q53HW5-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |
| http://purl.uniprot.org/uniprot/#_Q96IF9-mappedCitation-33381997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33381997 |