ArticleThe Journal of biological chemistry2010
The role of polyamines in supporting growth of mammalian cells is mediated through their requirement for translation initiation and elongation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 129 citations in OpenAlex.
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- The MFS transporter BcTpo1 governs the oxidative stress response and infection of Botrytis cinerea.Crop health · 2026Article
- Ubiquitously expressed prefoldin-like chaperone (UXT) regulates putrescine metabolism and promotes colorectal cancer progression.Human cell · 2026Article
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Solid-state cultivation-specific agmatine production by Aspergillus oryzae: current understanding and perspectives.Amino acids · 2026Review
- Inhibiting translation elongation by reducing eIF5A activity induces feedback inhibition of initiation, limiting tumour cell proliferation.Nature communications · 2025Article
- High-dose DFMO alters protein translation in neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- Preclinical Evaluation of the Efficacy of α-Difluoromethylornithine and Sulindac Against SARS-CoV-2 Infection.Viruses · 2025Article
- Spermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes.Science advances · 2025Article
- Biological Significance and Therapeutic Promise of Programmed Ribosomal Frameshifting.International journal of molecular sciences · 2025Review
- Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.The Journal of biological chemistry · 2025Article
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- Girolline is a sequence context-selective modulator of eIF5A activity.Nature communications · 2025Article
- Functional regulation of cytotoxic T cells by gut microbial metabolites.Gut microbes reports · 2025Article
- Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder-Robinson syndrome.Disease models & mechanisms · 2024Article
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
- Effects of Spermine Synthase Deficiency in Mesenchymal Stromal Cells Are Rescued by Upstream Inhibition of Ornithine Decarboxylase.International journal of molecular sciences · 2024Article
- New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape.Biology open · 2023Article
- Article
- Resolving Geroplasticity to the Balance of Rejuvenins and Geriatrins.Aging and disease · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Polyamines are essential cell constituents whose depletion results in growth cessation. Here we have investigated potential mechanisms of action of polyamines in supporting mammalian cell proliferation. We demonstrate that polyamines regulate translation both at the initiation and at the elongation steps. L-alpha-difluoromethylornithine treatment resulting in polyamine depletion reduces protein synthesis via inhibition of translation initiation. N1-guanyl-diaminoheptane (GC7), a spermidine analogue that inhibits eukaryotic initiation factor 5A (eIF5A) hypusination, also caused inhibition of translation initiation. In contrast, depletion of eIF5A by short hairpin RNA inhibits translation elongation as was recently demonstrated in yeast and Drosophila. These results suggest that in addition to competing with spermidine in the hypusination reaction, GC7 also competes with spermidine at yet undefined sites required for translation initiation. Finally, we show that either polyamine depletion or GC7 treatment induced eIF2alpha phosphorylation and reduced phosphorylation of 4E-BP, thus setting the molecular basis for the observed inhibition of translation initiation.
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Registered trials
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.