ArticleJournal of molecular biology2014
Novel interaction of ornithine decarboxylase with sepiapterin reductase regulates neuroblastoma cell proliferation.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- A novel lactylation-related gene signature deciphers the immunosuppressive microenvironment and stratifies precision therapy in colorectal cancer.Discover oncology · 2026Article
- Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis.Current medical science · 2024Article
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
- New role for GCH1 in cancer.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Article
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Tetrahydrobiopterin in Cell Function and Death Mechanisms.Antioxidants & redox signaling · 2022Review
- The Potential Role of Exosomal Proteins in Prostate Cancer.Frontiers in oncology · 2022Review
- Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.International journal of molecular sciences · 2021Article
- The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin.International journal of molecular sciences · 2021Review
- Polyamine Homeostasis in Development and Disease.Medical sciences (Basel, Switzerland) · 2021Review
- Sepiapterin reductase: Characteristics and role in diseases.Journal of cellular and molecular medicine · 2020Review
- Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas.Clinical and translational medicine · 2020Article
- The knockdown of the sepiapterin reductase gene suppresses the proliferation of breast cancer by inducing ROS-mediated apoptosis.International journal of clinical and experimental pathology · 2020Article
- Repurposing of Tranilast for Potential Neuropathic Pain Treatment by Inhibition of Sepiapterin Reductase in the BHACS omega · 2019Article
- Polyamine synthesis as a target ofThe Journal of biological chemistry · 2018Review
- A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon Amino Acid Starvation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Effect of sulfasalazine on human neuroblastoma: analysis of sepiapterin reductase (SPR) as a new therapeutic target.BMC cancer · 2015Article
- A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.PloS one · 2015Article
- Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Modulation of intestinal epithelial cell proliferation, migration, and differentiation in vitro by Astragalus polysaccharides.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Ornithine decarboxylase (ODC) is the sentinel enzyme in polyamine biosynthesis. Both ODC and polyamines regulate cell division, proliferation, and apoptosis. Sepiapterin reductase (SPR) catalyzes the last step in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, and has been implicated in neurological diseases but not yet in cancer. In this study, we present compelling evidence that native ODC and SPR physically interact, and we defined the individual amino acid residues involved in both enzymes using in silico protein-protein docking simulations. The resulting heterocomplex is a surprisingly compact structure, featuring two energetically and structurally equivalent binding modes both in monomer and in dimer conformations. The novel interaction between ODC and SPR proteins was confirmed under physiological conditions by co-immunoprecipitation and co-localization in neuroblastoma (NB) cells. Importantly, we showed that siRNA (small interfering RNA)-mediated knockdown of SPR expression significantly reduced endogenous ODC enzyme activity in NB cells, thus demonstrating the biological relevance of the ODC-SPR interaction. Finally, in a cohort of 88 human NB tumors, we found that high SPR mRNA expression correlated significantly with poor survival prognosis using a Kaplan-Meier analysis (log-rank test, P=5 × 10(-4)), suggesting an oncogenic role for SPR in NB tumorigenesis. In conclusion, we showed that ODC binds SPR and thus propose a new concept in which two well-characterized biochemical pathways converge via the interaction of two enzymes. We identified SPR as a novel regulator of ODC enzyme activity and, based on clinical evidence, present a model in which SPR drives ODC-mediated malignant progression in NB.
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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.