ArticleThe Journal of biological chemistry2011
1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2): a cautionary note on the anticancer mechanism of an eEF2 kinase inhibitor.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 114 citations in OpenAlex.
- Synaptic Potentiation in Hippocampus by eEF2K Inhibitor A484954.Hippocampus · 2026Article
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A dose-dependent switch in translation capacity controls the transcription factor response to HbioRxiv : the preprint server for biology · 2026Article
- Buparlisib induces eukaryotic elongation factor-2 expression to cause treatment failure for lung cancer cells.Molecular genetics and genomics : MGG · 2026Article
- Article
- eEF2K is a poor prognostic factor and novel molecular target in pancreatic cancer: regulating tumor growth and progression via the tumor microenvironment.Cell death & disease · 2025Article
- Regulation of translation elongation and integrated stress response in heat-shocked neurons.Cell reports · 2025Article
- Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Optimizing Human Cell-Free System for Efficient Protein Production.Journal of microbiology and biotechnology · 2025Article
- Elongation factor 2 in cancer: a promising therapeutic target in protein translation.Cellular & molecular biology letters · 2024Review
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Eukaryotic elongation factor 2 kinase inhibitor, A484954 induced diuresis via nitric oxide production in spontaneously hypertensive rats.The Journal of veterinary medical science · 2023Article
- IL-6 translation is a therapeutic target of human cytokine release syndrome.The Journal of experimental medicine · 2023Article
- Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.PLoS biology · 2023Article
- Roles of eukaryotic elongation factor 2 kinase (eEF2K) in neuronal plasticity, cognition, and Alzheimer disease.Journal of neurochemistry · 2023Review
- Structure of the complex between calmodulin and a functional construct of eukaryotic elongation factor 2 kinase bound to an ATP-competitive inhibitor.The Journal of biological chemistry · 2023Article
- Investigating Eukaryotic Elongation Factor 2 Kinase/Eukaryotic Translation Elongation Factor 2 Pathway Regulation and Its Role in Protein Synthesis Impairment during Disuse-Induced Skeletal Muscle Atrophy.The American journal of pathology · 2023Article
- Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.Cancer cell · 2023Article
- ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
7 more citing papers are in PubMed but not listed here.
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic elongation factor-2 kinase (eEF2K) relays growth and stress signals to protein synthesis through phosphorylation and inactivation of eukaryotic elongation factor 2 (eEF2). 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) is a widely accepted inhibitor of mammalian eEF2K and an efficacious anti-proliferation agent against different cancer cells. It implied that eEF2K could be an efficacious anticancer target. However, eEF2K siRNA was ineffective against cancer cells including those sensitive to NH125. To test if pharmacological intervention differs from siRNA interference, we identified a highly selective small molecule eEF2K inhibitor A-484954. Like siRNA, A-484954 had little effect on cancer cell growth. We carefully examined the effect of NH125 and A-484954 on phosphorylation of eEF2, the known cellular substrate of eEF2K. Surprisingly, NH125 increased eEF2 phosphorylation, whereas A-484954 inhibited the phosphorylation as expected for an eEF2K inhibitor. Both A-484954 and eEF2K siRNA inhibited eEF2K and reduced eEF2 phosphorylation with little effect on cancer cell growth. These data demonstrated clearly that the anticancer activity of NH125 was more correlated with induction of eEF2 phosphorylation than inhibition of eEF2K. Actually, induction of eEF2 phosphorylation was reported to correlate with inhibition of cancer cell growth. We compared several known inducers of eEF2 phosphorylation including AMPK activators and an mTOR inhibitor. Interestingly, stronger induction of eEF2 phosphorylation correlated with more effective growth inhibition. We also explored signal transduction pathways leading to NH125-induced eEF2 phosphorylation. Preliminary data suggested that NH125-induced eEF2 phosphorylation was likely mediated through multiple pathways. These observations identified an opportunity for a new multipathway approach to anticancer therapies.
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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.