| http://purl.uniprot.org/citations/27837025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27837025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27837025 | http://www.w3.org/2000/01/rdf-schema#comment | "Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ubiquitin ligase SCFFbxW7 However, N-Myc protein (the product of the MYCN oncogene) is stabilized in neuroblastoma by the protein kinase Aurora-A in a manner that is sensitive to certain Aurora-A-selective inhibitors. Here we identify a direct interaction between the catalytic domain of Aurora-A and a site flanking Myc Box I that also binds SCFFbxW7 We determined the crystal structure of the complex between Aurora-A and this region of N-Myc to 1.72-Å resolution. The structure indicates that the conformation of Aurora-A induced by compounds such as alisertib and CD532 is not compatible with the binding of N-Myc, explaining the activity of these compounds in neuroblastoma cells and providing a rational basis for the design of cancer therapeutics optimized for destabilization of the complex. We also propose a model for the stabilization mechanism in which binding to Aurora-A alters how N-Myc interacts with SCFFbxW7 to disfavor the generation of Lys48-linked polyubiquitin chains."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1610626113"xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1610626113"xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Bayliss R."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Bayliss R."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Burgess S.G."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Burgess S.G."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Carstensen A."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Carstensen A."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Chesler L."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Chesler L."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Eilers M."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Eilers M."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Poon E."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Poon E."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Richards M.W."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/author | "Richards M.W."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/pages | "13726-13731"xsd:string |
| http://purl.uniprot.org/citations/27837025 | http://purl.uniprot.org/core/pages | "13726-13731"xsd:string |