http://purl.uniprot.org/citations/27820802 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/27820802 | http://www.w3.org/2000/01/rdf-schema#comment | "RAS GTPases are important mediators of oncogenesis in humans. However, pharmacological inhibition of RAS has proved challenging. Here we describe a functionally critical region, located outside the effector lobe of RAS, that can be targeted for inhibition. We developed NS1, a synthetic binding protein (monobody) that bound with high affinity to both GTP- and GDP-bound states of H-RAS and K-RAS but not N-RAS. NS1 potently inhibited growth factor signaling and oncogenic H-RAS- and K-RAS-mediated signaling and transformation but did not block oncogenic N-RAS, BRAF or MEK1. NS1 bound the α4-β6-α5 region of RAS, which disrupted RAS dimerization and nanoclustering and led to blocking of CRAF-BRAF heterodimerization and activation. These results establish the importance of the α4-β6-α5 interface in RAS-mediated signaling and define a previously unrecognized site in RAS for inhibiting RAS function."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.org/dc/terms/identifier | "doi:10.1038/nchembio.2231"xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Jacobs M."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Sicheri F."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Smith M."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Zhou Y."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Ikura M."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Gupta A."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Koide S."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Koide A."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Lavoie H."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Dementieva I."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Sha F."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Therrien M."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Hancock J.F."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Dowdell E."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "O'Bryan J.P."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Herrero-Garcia E."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Rajakulendran T."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Okur M.N."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Eguchi R.R."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Cobbert J."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Gajwani P."xsd:string |
http://purl.uniprot.org/citations/27820802 | http://purl.uniprot.org/core/author | "Santana D."xsd:string |