ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
The Ubiquitin E3 Ligase TRAF6 Exacerbates Ischemic Stroke by Ubiquitinating and Activating Rac1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 85 citations in OpenAlex.
- Electroacupuncture Ameliorating Cerebral I/R-Induced Inflammatory Response through the TLR/TRAF6/NF-κB Pathway.Neurocritical care · 2026Article
- Non-canonical and constitutive activation of small GTPases: more than an exception to the rule?The Biochemical journal · 2026Review
- TRIM56 Aggravates Cerebral Ischemia-Reperfusion Injury via Inhibiting KLF4-Activated Ferroptosis Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Co-delivery of camptothecin and SH3RF3-AS1 SiRNA for glioma synergistic therapy.Cancer cell international · 2025Article
- Ubiquitylation-dependent Rap2 activation regulates lamellipodia dynamics during cell migration.Journal of cell science · 2025Article
- TXNIP Suppresses Lung Cancer Progression by Inhibiting TRAF6-Mediated NF-κB Activation and Autophagy.Immune network · 2025Article
- The Roles of E3 Ubiquitin Ligases in Cerebral Ischemia-Reperfusion Injury.International journal of molecular sciences · 2025Review
- BMSCs-derived exosomal Egr2 inhibited OGD/R-induced neuronal cell injury through the RNF8/DAPK1 axis in ischemic stroke.Experimental brain research · 2025Article
- Long Noncoding RNA ISA1 Protects Against Ischemic Brain Damage by Promoting the Transformation of Microglia Toward Anti-inflammatory Phenotype via the SOCS3/JAK2/STAT3 Pathway.Neurochemical research · 2025Article
- MiR-146a-5p downregulated TRAF6/NF-κB p65 pathway to attenuate the injury of HT-22 cells induced by oxygen-glucose deprivation/reoxygenation.In vitro cellular & developmental biology. Animal · 2025Article
- Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury.Molecular biology reports · 2024Review
- ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction.iScience · 2024Article
- Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.Clinical and translational medicine · 2024Review
- MiR-31-5p regulates the neuroinflammatory response via TRAF6 in neuropathic pain.Biology direct · 2024Article
- Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.Journal of Cancer · 2024Article
- Article
- Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke.Biomolecules · 2023Review
- Kaempferol counteracts bupivacaine-induced neurotoxicity in mouse dorsal root ganglia neurons by regulating TRAF6-dependent NF-κB signaling.The Kaohsiung journal of medical sciences · 2023Article
- IKK-mediated TRAF6 and RIPK1 interaction stifles cell death complex assembly leading to the suppression of TNF-α-induced cell death.Cell death and differentiation · 2023Article
- A comprehensive analysis of the hub genes for oxidative stress in ischemic stroke.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stroke is one of the leading causes of morbidity and mortality worldwide. Inflammation, oxidative stress, apoptosis, and excitotoxicity contribute to neuronal death during ischemic stroke; however, the mechanisms underlying these complicated pathophysiological processes remain to be fully elucidated. Here, we found that the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) was markedly increased after cerebral ischemia/reperfusion (I/R) in mice. TRAF6 ablation in male mice decreased the infarct volume and neurological deficit scores and decreased proinflammatory signaling, oxidative stress, and neuronal death after cerebral I/R, whereas transgenic overexpression of TRAF6 in male mice exhibited the opposite effects. Mechanistically, we demonstrated that TRAF6 induced Rac1 activation and consequently promoted I/R injury by directly binding and ubiquitinating Rac1. Either functionally mutating the TRAF6 ubiquitination site on Rac1 or inactivating Rac1 with a specific inhibitor reversed the deleterious effects of TRAF6 overexpression during I/R injury. In conclusion, our study demonstrated that TRAF6 is a key promoter of ischemic signaling cascades and neuronal death after cerebral I/R injury. Therefore, the TRAF6/Rac1 pathway might be a promising target to attenuate cerebral I/R injury.
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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.