ArticleThe Journal of biological chemistry2015
Biological Relevance and Therapeutic Potential of the Hypusine Modification System.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- A gene therapy strategy for Deoxyhypusine Synthase (DHPS) syndrome.Research square · 2026Article
- Article
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- Sustained-Release Spermidine Hydrogel Inhibits M1 Macrophage Polarization and Promotes Tissue Repair for Spinal Cord Injury Repair.Biomaterials research · 2025Article
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
- Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.JCI insight · 2023Article
- An MYC-Driven Vicious Circuit Is a Targetable Achilles' Heel in Lymphoma.Blood cancer discovery · 2023Article
- The Polyamine-Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma.Blood cancer discovery · 2023Article
- New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape.Biology open · 2023Article
- Eukaryotic Initiation Factor 5A2 localizes to actively translating ribosomes to promote cancer cell protrusions and invasive capacity.Cell communication and signaling : CCS · 2023Article
- Research Progress and Potential Applications of Spermidine in Ocular Diseases.Pharmaceutics · 2022Review
- Post-translational formation of hypusine in eIF5A: implications in human neurodevelopment.Amino acids · 2022Review
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Article
- The role of polyamines in gastric cancer.Oncogene · 2021Review
- Polyamines: Functions, Metabolism, and Role in Human Disease Management.Medical sciences (Basel, Switzerland) · 2021Review
- EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway.Cell & bioscience · 2021Article
- Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine.Nature communications · 2021Article
- Arginine, Agmatine, and Polyamines: Key Regulators of Conceptus Development in Mammals.Advances in experimental medicine and biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is emerging as a crucial regulator in cancer, infections, and inflammation. Although its contribution in translational regulation of proline repeat-rich proteins has been sufficiently demonstrated, its biological role in higher eukaryotes remains poorly understood. To establish the hypusine modification system as a novel platform for therapeutic strategies, we aimed to investigate its functional relevance in mammals by generating and using a range of new knock-out mouse models for the hypusine-modifying enzymes deoxyhypusine synthase and deoxyhypusine hydroxylase as well as for the cancer-related isoform eIF-5A2. We discovered that homozygous depletion of deoxyhypusine synthase and/or deoxyhypusine hydroxylase causes lethality in adult mice with different penetrance compared with haploinsufficiency. Network-based bioinformatic analysis of proline repeat-rich proteins, which are putative eIF-5A targets, revealed that these proteins are organized in highly connected protein-protein interaction networks. Hypusine-dependent translational control of essential proteins (hubs) and protein complexes inside these networks might explain the lethal phenotype observed after deletion of hypusine-modifying enzymes. Remarkably, our results also demonstrate that the cancer-associated isoform eIF-5A2 is dispensable for normal development and viability. Together, our results provide the first genetic evidence that the hypusine modification in eIF-5A is crucial for homeostasis in mammals. Moreover, these findings highlight functional diversity of the hypusine system compared with lower eukaryotes and indicate eIF-5A2 as a valuable and safe target for therapeutic intervention in cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.