| http://purl.uniprot.org/citations/37317963 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37317963 | http://www.w3.org/2000/01/rdf-schema#comment | "RAS mutations are among the most prevalent oncogenic drivers in cancers. RAS proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. Here, we discovered that RAB27B, a RAB family small GTPase, controlled NRAS palmitoylation and trafficking to the plasma membrane, a localization required for activation. Our proteomic studies revealed RAB27B upregulation in CBL- or JAK2-mutated myeloid malignancies, and its expression correlated with poor prognosis in acute myeloid leukemias (AMLs). RAB27B depletion inhibited the growth of CBL-deficient or NRAS-mutant cell lines. Strikingly, Rab27b deficiency in mice abrogated mutant but not WT NRAS-mediated progenitor cell growth, ERK signaling, and NRAS palmitoylation. Further, Rab27b deficiency significantly reduced myelomonocytic leukemia development in vivo. Mechanistically, RAB27B interacted with ZDHHC9, a palmitoyl acyltransferase that modifies NRAS. By regulating palmitoylation, RAB27B controlled c-RAF/MEK/ERK signaling and affected leukemia development. Importantly, RAB27B depletion in primary human AMLs inhibited oncogenic NRAS signaling and leukemic growth. We further revealed a significant correlation between RAB27B expression and sensitivity to MEK inhibitors in AMLs. Thus, our studies presented a link between RAB proteins and fundamental aspects of RAS posttranslational modification and trafficking, highlighting future therapeutic strategies for RAS-driven cancers."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci165510"xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Wu M."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Tong W."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Wang R."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Lv K."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Xing B."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Philips M.R."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "O'Keefe R.A."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Ren J.G."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "O'Connell R.M."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Ghazaryan A."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Bauer K.M."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Pillai V."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Hexner E.O."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/author | "Burslem G.M."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/pages | "e165510"xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/title | "RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia."xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://purl.uniprot.org/core/volume | "133"xsd:string |
| http://purl.uniprot.org/citations/37317963 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37317963 |
| http://purl.uniprot.org/citations/37317963 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37317963 |