ArticleDisease models & mechanisms2014
A novel mouse model for inhibition of DOHH-mediated hypusine modification reveals a crucial function in embryonic development, proliferation and oncogenic transformation.
Article in Disease models & mechanisms, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Axonal Eif5a hypusination controls local translation and mitigates defects in FUS-ALS.Nature neuroscience · 2026Article
- Case Report: A new patient expanding the clinical spectrum ofFrontiers in pediatrics · 2026Article
- 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
- Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons.Molecular brain · 2024Article
- 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
- Structural Insights into the Mechanisms Underlying Polyaminopathies.International journal of molecular sciences · 2024Review
- Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis.HGG advances · 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
- Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8Nature communications · 2022Article
- Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.American journal of human genetics · 2022Article
- Post-translational formation of hypusine in eIF5A: implications in human neurodevelopment.Amino acids · 2022Review
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production.Frontiers in cellular and infection microbiology · 2022Article
- Article
- Polyamines: Functions, Metabolism, and Role in Human Disease Management.Medical sciences (Basel, Switzerland) · 2021Review
- Arginine, Agmatine, and Polyamines: Key Regulators of Conceptus Development in Mammals.Advances in experimental medicine and biology · 2021Article
- Eukaryotic translation initiation factor 5A in the pathogenesis of cancers.Oncology letters · 2020Review
- KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation.PloS one · 2020Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The central importance of translational control by post-translational modification has spurred major interest in regulatory pathways that control translation. One such pathway uniquely adds hypusine to eukaryotic initiation factor 5A (eIF5A), and thereby affects protein synthesis and, subsequently, cellular proliferation through an unknown mechanism. Using a novel conditional knockout mouse model and a Caenorhabditis elegans knockout model, we found an evolutionarily conserved role for the DOHH-mediated second step of hypusine synthesis in early embryonic development. At the cellular level, we observed reduced proliferation and induction of senescence in 3T3 Dohh-/- cells as well as reduced capability for malignant transformation. Furthermore, mass spectrometry showed that deletion of DOHH results in an unexpected complete loss of hypusine modification. Our results provide new biological insight into the physiological roles of the second step of the hypusination of eIF5A. Moreover, the conditional mouse model presented here provides a powerful tool for manipulating hypusine modification in a temporal and spatial manner, to analyse both how this unique modification normally functions in vivo as well as how it contributes to different pathological conditions.
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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.