ArticleJournal of neurochemistry2009
Mutant copper-zinc superoxide dismutase associated with amyotrophic lateral sclerosis binds to adenine/uridine-rich stability elements in the vascular endothelial growth factor 3'-untranslated region.
Article in Journal of neurochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.Journal of molecular neuroscience : MN · 2025Article
- Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.International journal of molecular sciences · 2023Article
- Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.International journal of molecular sciences · 2023Article
- Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors.Cancers · 2022Review
- The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.Advanced drug delivery reviews · 2022Review
- Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).Wiley interdisciplinary reviews. RNA · 2020Review
- Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants.Frontiers in neurology · 2019Review
- Hu antigen R (HuR) is a positive regulator of the RNA-binding proteins TDP-43 and FUS/TLS: implications for amyotrophic lateral sclerosis.The Journal of biological chemistry · 2014Article
- Gene and protein therapies utilizing VEGF for ALS.Pharmacology & therapeutics · 2014Review
- From Transcriptome to Noncoding RNAs: Implications in ALS Mechanism.Neurology research international · 2012Article
- The complex molecular biology of amyotrophic lateral sclerosis (ALS).Progress in molecular biology and translational science · 2012Review
- HuR function in disease.Frontiers in bioscience (Landmark edition) · 2012Review
- DNA-triggered aggregation of copper, zinc superoxide dismutase in the presence of ascorbate.PloS one · 2010Article
- RNA processing pathways in amyotrophic lateral sclerosis.Neurogenetics · 2010Review
- Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.Human molecular genetics · 2010Article
- Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor.The Journal of biological chemistry · 2009Article
- Genetics of motor neuron disorders: new insights into pathogenic mechanisms.Nature reviews. Genetics · 2009Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) is a neurotrophic factor essential for maintenance of motor neurons. Loss of this factor produces a phenotype similar to amyotrophic lateral sclerosis (ALS). We recently showed that ALS-producing mutations of Cu/Zn-superoxide dismutase (SOD1) disrupt post-transcriptional regulation of VEGF mRNA, leading to significant loss of expression [Lu et al., J. Neurosci.27 (2007), 7929]. Mutant SOD1 was present in the ribonucleoprotein complex associated with adenine/uridine-rich elements (ARE) of the VEGF 3'-untranslated region (UTR). Here, we show by electrophoretic mobility shift assay that mutant SOD1 bound directly to the VEGF 3'-UTR with a predilection for AREs similar to the RNA stabilizer HuR. SOD1 mutants A4V and G37R showed higher affinity for the ARE than L38V or G93A. Wild-type SOD1 bound very weakly with an apparent K(d) 11- to 72-fold higher than mutant forms. Mutant SOD1 showed an additional lower shift with VEGF ARE that was accentuated in the metal-free state. A similar pattern of binding was observed with AREs of tumor necrosis factor-alpha and interleukin-8, except only a single shift predominated. Using an ELISA-based assay, we demonstrated that mutant SOD1 competes with HuR and neuronal HuC for VEGF 3'-UTR binding. To define potential RNA-binding domains, we truncated G37R, G93A and wild-type SOD1 and found that peptides from the N-terminal portion of the protein that included amino acids 32-49 could recapitulate the binding pattern of full-length protein. Thus, the strong RNA-binding affinity conferred by ALS-associated mutations of SOD1 may contribute to the post-transcriptional dysregulation of VEGF mRNA.
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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.