ArticleBlood2020
Genetic disruption of N-RasG12D palmitoylation perturbs hematopoiesis and prevents myeloid transformation in mice.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Proteome-Wide Analysis of Palmitoylated Proteins in Macrophages Reveals Novel Insights Into Early Immune Signaling.Proteomics · 2026Article
- De novo design of Ras isoform selective binders.Cell chemical biology · 2026Article
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- Protein palmitoylation in hematological malignancies: mechanistic links to lipid metabolic reprogramming and therapy resistance.Frontiers in immunology · 2026Review
- Rac1 palmitoylation is required for cardiac stress adaptation and regulation of protein kinase A signaling.JCI insight · 2025Article
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Rab3gap1 palmitoylation cycling modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.Biophysical journal · 2025Article
- Positive feedback loop between NRASBiochemical and biophysical research communications · 2025Article
- Article
- ZDHHC18 promotes renal fibrosis development by regulating HRAS palmitoylation.The Journal of clinical investigation · 2025Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation.Nature structural & molecular biology · 2024Article
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- GOLGA7 is essential for NRAS trafficking from the Golgi to the plasma membrane but not for its palmitoylation.Cell communication and signaling : CCS · 2024Article
- Palmitoylation landscapes across human cancers reveal a role of palmitoylation in tumorigenesis.Journal of translational medicine · 2023Article
- RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia.The Journal of clinical investigation · 2023Article
- Identification ofInternational journal of molecular sciences · 2022Article
- Post-translational modification of RAS proteins.Current opinion in structural biology · 2021Review
- ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth.Nature chemical biology · 2021Article
- Dual regulation of fatty acid synthase (FASN) expression by O-GlcNAc transferase (OGT) and mTOR pathway in proliferating liver cancer cells.Cellular and molecular life sciences : CMLS · 2021Article
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13 authors at 4 institutions in 1 country.
Funding
Abstract
Oncogenic RAS mutations pose substantial challenges for rational drug discovery. Sequence variations within the hypervariable region of Ras isoforms underlie differential posttranslational modification and subcellular trafficking, potentially resulting in selective vulnerabilities. Specifically, inhibiting the palmitoylation/depalmitoylation cycle is an appealing strategy for treating NRAS mutant cancers, particularly as normal tissues would retain K-Ras4b function for physiologic signaling. The role of endogenous N-RasG12D palmitoylation in signal transduction, hematopoietic differentiation, and myeloid transformation is unknown, and addressing these key questions will inform efforts to develop mechanism-based therapies. To evaluate the palmitoylation/depalmitoylation cycle as a candidate drug target in an in vivo disease-relevant model system, we introduced a C181S mutation into a conditional NrasG12D "knock-in" allele. The C181S second-site amino acid substitution abrogated myeloid transformation by NrasG12D, which was associated with mislocalization of the nonpalmitoylated N-Ras mutant protein, reduced Raf/MEK/ERK signaling, and alterations in hematopoietic stem and progenitor populations. Furthermore, hematologic malignancies arising in NrasG12D/G12D,C181S compound heterozygous mice invariably acquired revertant mutations that restored cysteine 181. Together, these studies validate the palmitoylation cycle as a promising therapeutic target in NRAS mutant 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.