ArticleBlood cancer discovery2023
The Polyamine-Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma.
Article in Blood cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase.Communications chemistry · 2026Article
- Hsa_circ_0003611 hinders the transformation of mesenchymal stem cells into osteosarcoma cells through suppressing MYC by IGF2BP3 via mBiological research · 2025Article
- Article
- High-dose DFMO alters protein translation in neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- eIF5A maintains intestinal epithelial homeostasis by sustaining intestinal stem cells.Cell regeneration (London, England) · 2025Article
- Polyamine metabolism in prostate cancer.Current opinion in oncology · 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
- Spermidine metabolism regulates leukemia stem and progenitor cell function through KAT7 expression in patient-derived mouse models.Science translational medicine · 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
- Polyamines: Key Players in Immunometabolism and Immune Regulation.Journal of cellular immunology · 2024Article
- An MYC-Driven Vicious Circuit Is a Targetable Achilles' Heel in Lymphoma.Blood cancer discovery · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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Abstract
The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine-hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where the loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA sequencing, ribosome sequencing, and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1-S phase cell-cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types. SIGNIFICANCE: Elevated EIF5A and the polyamine-hypusine circuit are manifest in many malignancies, including MYC-driven tumors, and eIF5A hypusination is necessary for MYC proliferative signaling. Not-ably, this circuit controls an oncogenic translational program essential for the development and maintenance of MYC-driven lymphoma, supporting this axis as a target for cancer prevention and treatment. See related commentary by Wilson and Klein, p. 248. This article is highlighted in the In This Issue feature, p. 247.
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