ArticleCell death and differentiation2012
WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3β.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 57 citations in OpenAlex.
- Neuron-specific WWOX gene therapy produces dose-dependent, durable rescue in a model of WWOX-related epileptic encephalopathy.Molecular therapy. Advances · 2026Article
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- Alzheimer's disease risk geneBrain communications · 2026Article
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- Molecular Mechanism of WWOX Inhibiting the Development of Esophageal Cancer by Inhibiting Hippo Signaling Pathway.Biochemical genetics · 2025Article
- Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with sleep duration.Scientific reports · 2025Article
- HN1 is a novel dedifferentiation factor involved in regulating the cell cycle and microtubules in SH-SY5Y neuroblastoma cells.Journal of cellular biochemistry · 2025Article
- Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration.International journal of molecular sciences · 2024Review
- Neuroimaging features of WOREE syndrome: a mini-review of the literature.Frontiers in pediatrics · 2023Review
- Glycogen Synthase Kinase-3 Interaction Domain Enhances Phosphorylation of SARS-CoV-2 Nucleocapsid Protein.Molecules and cells · 2022Article
- Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration.International journal of molecular sciences · 2022Article
- Review
- Article
- Article
- New Era of Mapping and Understanding Common Fragile Sites: An Updated Review on Origin of Chromosome Fragility.Frontiers in genetics · 2022Review
- Review
- Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy.Life (Basel, Switzerland) · 2021Review
- Modeling genetic epileptic encephalopathies using brain organoids.EMBO molecular medicine · 2021Article
- Review
- Neurological Disorders Associated with WWOX Germline Mutations-A Comprehensive Overview.Cells · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
WW domain-containing oxidoreductase (WWOX), a putative tumour suppressor, is suggested to be involved in the hyperphosphorylation of Alzheimer's Tau. Tau is a microtubule-associated protein that has an important role in microtubule assembly and stability. Glycogen synthase kinase 3β (GSK3β) has a vital role in Tau hyperphosphorylation at its microtubule-binding domains. Hyperphosphorylated Tau has a low affinity for microtubules, thus disrupting microtubule stability. Bioinformatics analysis indicated that WWOX contains two potential GSK3β-binding FXXXLI/VXRLE motifs. Immunofluorescence, immunoprecipitation and molecular modelling showed that WWOX interacts physically with GSK3β. We demonstrated biochemically that WWOX can bind directly to GSK3β through its short-chain alcohol dehydrogenase/reductase domain. Moreover, the overexpression of WWOX inhibited GSK3β-stimulated S396 and S404 phosphorylation within the microtubule domains of Tau, indicating that WWOX is involved in regulating GSK3β activity in cells. WWOX repressed GSK3β activity, restored the microtubule assembly activity of Tau and promoted neurite outgrowth in SH-SY5Y cells. Conversely, RNAi-mediated knockdown of WWOX in retinoic acid (RA)-differentiated SH-SY5Y cells inhibited neurite outgrowth. These results suggest that WWOX is likely to be involved in regulating GSK3β activity, reducing the level of phosphorylated Tau, and subsequently promoting neurite outgrowth during neuron differentiation. In summary, our data reveal a novel mechanism by which WWOX promotes neuronal differentiation in response to RA.
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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.