ArticleLife science alliance2021
NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane.
Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- Very Long Chain Fatty Acid Synthesis is a Targetable Dependency in RAS Pathway Mutant Leukemia.Blood cancer discovery · 2026Article
- Loss of Golga7 Suppresses Oncogenic Nras-Driven Leukemogenesis without Detectable Toxicity in Adult Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Specific Disruption of Ras2 CAAX Proteolysis Alters Its Localization and Function.Microbiology spectrum · 2023Article
- Pathway-based approach reveals differential sensitivity to E2F1 inhibition in glioblastoma.Cancer research communications · 2022Article
- Signaling in the crowded cell.Current opinion in structural biology · 2021Review
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Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Isoprenylcysteine carboxyl methyltransferase (ICMT) is the third of three enzymes that sequentially modify the C-terminus of CaaX proteins, including RAS. Although all four RAS proteins are substrates for ICMT, each traffics to membranes differently by virtue of their hypervariable regions that are differentially palmitoylated. We found that among RAS proteins, NRAS was unique in requiring ICMT for delivery to the PM, a consequence of having only a single palmitoylation site as its secondary affinity module. Although not absolutely required for palmitoylation, acylation was diminished in the absence of ICMT. Photoactivation and FRAP of GFP-NRAS revealed increase flux at the Golgi, independent of palmitoylation, in the absence of ICMT. Association of NRAS with the prenyl-protein chaperone PDE6δ also required ICMT and promoted anterograde trafficking from the Golgi. We conclude that carboxyl methylation of NRAS is required for efficient palmitoylation, PDE6δ binding, and homeostatic flux through the Golgi, processes that direct delivery to the plasma membrane.
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Registered trials
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