ArticleScientific reports2016
VRK3-mediated nuclear localization of HSP70 prevents glutamate excitotoxicity-induced apoptosis and Aβ accumulation via enhancement of ERK phosphatase VHR activity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response.PLoS pathogens · 2026Article
- Emergence of Catalytic Activity in VRK3: Phosphoproteomic Insights into the Regulatory Network of a Former Pseudokinase.Proteomes · 2026Review
- Selective autophagy inhibition alleviates oxidative stress-associated neurodegeneration in an AD+CCH model.Frontiers in aging neuroscience · 2026Article
- Tensor decomposition of multi-dimensional splicing events across multiple tissues to identify splicing-mediated risk genes associated with complex traits.PLoS computational biology · 2025Article
- Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease.Cells · 2025Review
- M2 Microglia-Derived Exosomes Protect Against Glutamate-Induced HT22 Cell Injury via Exosomal miR-124-3p.Molecular neurobiology · 2024Article
- Inhalation Anesthetics Play a Janus-Faced Role in Self-Renewal and Differentiation of Stem Cells.Biomolecules · 2024Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- A brain proteomic signature of incipient Alzheimer's disease in youngScience advances · 2021Article
- The Hsp70 chaperone system: distinct roles in erythrocyte formation and maintenance.Haematologica · 2021Review
- Trypanosoma brucei RAP1 Has Essential Functional Domains That Are Required for Different Protein Interactions.mSphere · 2020Article
- Article
- A novel cell-penetrating peptide protects against neuron apoptosis after cerebral ischemia by inhibiting the nuclear translocation of annexin A1.Cell death and differentiation · 2019Article
- MicroRNA-219 alleviates glutamate-induced neurotoxicity in cultured hippocampal neurons by targeting calmodulin-dependent protein kinase II gamma.Neural regeneration research · 2018Article
- Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer.Molecules and cells · 2017Article
- Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most of neurodegenerative disorders are associated with protein aggregation. Glutamate-induced excitotoxicity and persistent extracellular signal-regulated kinase (ERK) activation are also implicated in neurodegenerative diseases. Here, we found that vaccinia-related kinase 3 (VRK3) facilitates nuclear localization of glutamate-induced heat shock protein 70 (HSP70). Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Moreover, glutamate-induced ERK activation stimulates the expression of HSP70 and VRK3 at the transcriptional level. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis. Overexpression of HSP70 fused to a nuclear localization signal attenuated apoptosis more than HSP70 alone. The importance of nuclear localization of HSP70 in the negative regulation of glutamate-induced ERK activation was further confirmed in VRK3-deficient neurons. Importantly, we showed a positive correlation between levels of VRK3 and HSP70 in the progression of Alzheimer's and Parkinson's diseases in humans, and neurons with HSP70 nuclear localization exhibited less Aβ accumulation in brains from patients with Alzheimer's disease. Therefore, HSP70 and VRK3 could potentially serve as diagnostic and therapeutic targets in neurodegenerative diseases.
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