| http://purl.uniprot.org/citations/23633493 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23633493 | http://www.w3.org/2000/01/rdf-schema#comment | "Deregulation of the mTOR pathway is closely associated with tumorigenesis. Accordingly, mTOR inhibitors such as rapamycin and mTOR-selective kinase inhibitors have been tested as cancer therapeutic agents. Inhibition of mTOR results in sensitization to DNA-damaging agents; however, the molecular mechanism is not well understood. We found that an mTOR-selective kinase inhibitor, AZD8055, significantly enhanced sensitivity of a pediatric rhabdomyosarcoma xenograft to radiotherapy and sensitized rhabdomyosarcoma cells to the DNA interstrand cross-linker (ICL) melphalan. Sensitization correlated with drug-induced downregulation of a key component of the Fanconi anemia pathway, FANCD2 through mTOR regulation of FANCD2 gene transcripts via mTORC1-S6K1. Importantly, we show that FANCD2 is required for the proper activation of ATM-Chk2 checkpoint in response to ICL and that mTOR signaling promotes ICL-induced ATM-Chk2 checkpoint activation by sustaining FANCD2. In FANCD2-deficient lymphoblasts, FANCD2 is essential to suppress endogenous and induced DNA damage, and FANCD2-deficient cells showed impaired ATM-Chk2 and ATR-Chk1 activation, which was rescued by reintroduction of wild-type FANCD2. Pharmacologic inhibition of PI3K-mTOR-AKT pathway in Rh30 rhabdomyosarcoma cells attenuated ICL-induced activation of ATM, accompanied with the decrease of FANCD2. These data suggest that the mTOR pathway may promote the repair of DNA double-strand breaks by sustaining FANCD2 and provide a novel mechanism of how the Fanconi anemia pathway modulates DNA damage response and repair."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-12-4282"xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Shen C."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Pang Q."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Cam H."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Phelps D."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Oswald D."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Houghton P.J."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/author | "Pelloski C.E."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/pages | "3393-3401"xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/title | "Regulation of FANCD2 by the mTOR pathway contributes to the resistance of cancer cells to DNA double-strand breaks."xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://purl.uniprot.org/core/volume | "73"xsd:string |
| http://purl.uniprot.org/citations/23633493 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23633493 |
| http://purl.uniprot.org/citations/23633493 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23633493 |
| http://purl.uniprot.org/uniprot/#_Q9BXW9-mappedCitation-23633493 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23633493 |
| http://purl.uniprot.org/uniprot/Q9BXW9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23633493 |