| http://purl.uniprot.org/citations/30712867 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30712867 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30712867 | http://www.w3.org/2000/01/rdf-schema#comment | "Activating mutations in NRAS account for 20%-30% of melanoma, but despite decades of research and in contrast to BRAF, no effective anti-NRAS therapies have been forthcoming. Here, we identify a previously uncharacterized serine/threonine kinase STK19 as a novel NRAS activator. STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation. A recurrent D89N substitution in STK19 whose alterations were identified in 25% of human melanomas represents a gain-of-function mutation that interacts better with NRAS to enhance melanocyte transformation. STK19D89N knockin leads to skin hyperpigmentation and promotes NRASQ61R-driven melanomagenesis in vivo. Finally, we developed ZT-12-037-01 (1a) as a specific STK19-targeted inhibitor and showed that it effectively blocks oncogenic NRAS-driven melanocyte malignant transformation and melanoma growth in vitro and in vivo. Together, our findings provide a new and viable therapeutic strategy for melanomas harboring NRAS mutations."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2019.01.002"xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2019.01.002"xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Chen S."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Chen S."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Gao X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Gao X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Liu T."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Liu T."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Huang C."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Huang C."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Wei G."xsd:string |
| http://purl.uniprot.org/citations/30712867 | http://purl.uniprot.org/core/author | "Wei G."xsd:string |