| http://purl.uniprot.org/citations/35104933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35104933 | http://www.w3.org/2000/01/rdf-schema#comment | "RAS is a major anticancer drug target which requires membrane localization to activate downstream signal transduction. The direct inhibition of RAS has proven to be challenging. Here, we present a novel strategy for targeting RAS by stabilizing its interaction with the prenyl-binding protein PDE6D and disrupting its localization. Using rationally designed RAS point mutations, we were able to stabilize the RAS:PDE6D complex by increasing the affinity of RAS for PDE6D, which resulted in the redirection of RAS to the cytoplasm and the primary cilium and inhibition of oncogenic RAS/ERK signaling. We developed an SPR fragment screening and identified fragments that bind at the KRAS:PDE6D interface, as shown through cocrystal structures. Finally, we show that the stoichiometric ratios of KRAS:PDE6D vary in different cell lines, suggesting that the impact of this strategy might be cell-type-dependent. This study forms the foundation from which a potential anticancer small-molecule RAS:PDE6D complex stabilizer could be developed."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.org/dc/terms/identifier | "doi:10.1021/acs.jmedchem.1c01265"xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Garcia E."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Parry C."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Yu Q."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Kowalczyk D."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Ismail S."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Cameron K."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Bower J."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Goodwin G."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Chen Y.X."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Pugliese A."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Jamieson A."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "McArthur D."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Zhu P.C."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Wojnowska M."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Yelland T."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Gohlke A."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Zalar M."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "ElMaghloob Y."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/author | "Archibald L."xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/name | "J Med Chem"xsd:string |
| http://purl.uniprot.org/citations/35104933 | http://purl.uniprot.org/core/pages | "1898-1914"xsd:string |