ArticleRedox biology2020
Role of WW domain E3 ubiquitin protein ligase 2 in modulating ubiquitination and Degradation of Septin4 in oxidative stress endothelial injury.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Genome-Wide Association Study of Corneal Dystrophy Uncovers Novel Risk Loci and Enables Improved Polygenic Prediction of Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Pooled it
- Large-scale cross-ancestry genome-wide meta-analysis of serum urate.Nature communications · 2024Pooled it
- The ubiquitin system in heart and vessel pathobiology: From mechanisms to therapeutic strategies.Genes & diseases · 2026Review
- E3 Ubiquitin Ligase UBR5 Aggravates Cardiac Hypertrophy Via Inhibiting Nrf2/HO-1 Pathway.Cardiovascular drugs and therapy · 2026Article
- Endothelial dysfunction in human diabetic vascular complications: translating single-cell transcriptomics into therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- Genome-wide association study of corneal dystrophy uncovers novel risk loci and enables improved polygenic prediction of Fuchs endothelial corneal dystrophy.medRxiv : the preprint server for health sciences · 2026Article
- Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications.Current issues in molecular biology · 2025Review
- New Types of Post-Translational Modification of Proteins in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- The Ubiquitination and Degradation of SH2B3 Mediated by MEF2A/WWP2 Axis Restores Microglial Homeostasis to Alleviate Cerebral Microvascular Endothelial Cell Injury in Ischemic Stroke.Neurochemical research · 2025Article
- CircBTBD7-420aa Encoded by hsa_circ_0000563 Regulates the Progression of Atherosclerosis and Construction of circBTBD7-420aa Engineered Exosomes.JACC. Basic to translational science · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- XPNPEP2 regulates angiogenesis via modulation of mitochondrial function through SLC25A6.Frontiers in cell and developmental biology · 2025Article
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
- TFEB promotes Ginkgetin-induced ferroptosis via TRIM25 mediated GPX4 lysosomal degradation in EGFR wide-type lung adenocarcinoma.Theranostics · 2025Article
- Evaluation of microRNA expression profiles in human sperm frozen using permeable cryoprotectant-free droplet vitrification and conventional methods.Asian journal of andrology · 2024Article
- Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells.The Journal of cell biology · 2024Article
- WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis.Journal of translational internal medicine · 2024Article
- The correlation of Septin4 gene expression with sperm quality, DNA damage, and oxidative stress level in infertile patients.Anatomy & cell biology · 2023Article
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA.Signal transduction and targeted therapy · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress-associated endothelial injury is the initial event and major cause of multiple cardiovascular diseases such as atherosclerosis and hypertensive angiopathy. A protein homeostasis imbalance is a critical cause of endothelial injury, and homologous to E6AP C-terminus (HECT)-type E3 ubiquitin ligases are the core factors controlling protein homeostasis. Although HECT-type E3 ubiquitin ligases are involved in the regulation of cardiac development and diseases, their roles in endothelial injury remain largely unknown. This study aimed to identify which HECT-type E3 ubiquitin ligase is involved in endothelial injury and clarify the mechanisms at molecular, cellular, and organism levels. We revealed a novel role of the HECT-type E3 ubiquitin ligase WWP2 in regulating endothelial injury and vascular remodeling after endothelial injury. Endothelial/myeloid-specific WWP2 knockout in mice significantly aggravated angiotensin II/oxidative stress-induced endothelial injury and vascular remodeling after endothelial injury. The same results were obtained from in vitro experiments. Mechanistically, the endothelial injury factor Septin4 was identified as a novel physiological substrate of WWP2. In addition, WWP2 interacted with the GTPase domain of Septin4, ubiquitinating Septin4-K174 to degrade Septin4 through the ubiquitin-proteasome system, which inhibited the Septin4-PARP1 endothelial damage complex. These results identified the first endothelial injury-associated physiological pathway regulated by HECT-type E3 ubiquitin ligases in vivo as well as a unique proteolytic mechanism through which WWP2 controls endothelial injury and vascular remodeling after endothelial injury. These findings might provide a novel treatment strategy for oxidative stress-associated atherosclerosis and hypertensive vascular diseases.
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Registered trials
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