ArticleThe Journal of clinical investigation2023
RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Rab27: Molecular switch of tumor exosome secretion (Review).International journal of molecular medicine · 2026Review
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Article
- The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans.Scientific reports · 2026Article
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- Palmitic acid activates c-Myc via dual palmitoylation-dependent pathways to promote colon cancer.Cell discovery · 2026Article
- ZDHHC4-mediated ZEB-2 S-palmitoylation promotes melanoma epithelial-mesenchymal transition via deubiquitinating and stabilizing ZEB-2.Cellular and molecular life sciences : CMLS · 2026Article
- Convergent Multistage Evidence Implicates the CCR2-Artemin Immune-Inflammation Axis in Acute Myeloid Leukemia.Mediators of inflammation · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Exploring the role of palmitoylation-related genes in atrial fibrillation and analysis of immune cell infiltration.Medicine · 2025Article
- Role of the RAB27/SYTL Axis in Tumor Microenvironment Construction.Cancer science · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity.Science advances · 2025Article
- Acyl post-translational modification of proteins by metabolites in cancer cells.Cell death discovery · 2025Review
- Loss of Golga7 Suppresses Oncogenic Nras-Driven Leukemogenesis without Detectable Toxicity in Adult Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetically druggable targets for MAPK-activated colorectal cancer by a two-sample mendelian randomization analysis.Scientific reports · 2025Article
- ZDHHC9-mediated CD38 palmitoylation stabilizes CD38 expression and promotes pancreatic cancer growth.Communications biology · 2025Article
- Revealing the role of RAB27 in HER receptor family expression and signaling in melanoma cells.Cell communication and signaling : CCS · 2025Article
- Functional Role of Fatty Acid Synthase for Signal Transduction in Core-Binding Factor Acute Myeloid Leukemia with an Activating c-Kit Mutation.Biomedicines · 2025Article
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15 authors at 5 institutions in 2 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.