| http://purl.uniprot.org/citations/31924572 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31924572 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.redox.2019.101419"xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/author | "Zhang N."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/author | "Wu B."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/author | "You S."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/name | "Redox Biol"xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/pages | "101419"xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/title | "Role of WW domain E3 ubiquitin protein ligase 2 in modulating ubiquitination and Degradation of Septin4 in oxidative stress endothelial injury."xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://purl.uniprot.org/core/volume | "30"xsd:string |
| http://purl.uniprot.org/citations/31924572 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31924572 |
| http://purl.uniprot.org/citations/31924572 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31924572 |
| http://purl.uniprot.org/uniprot/#_B4DIN7-mappedCitation-31924572 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31924572 |
| http://purl.uniprot.org/uniprot/#_B4DHF6-mappedCitation-31924572 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31924572 |
| http://purl.uniprot.org/uniprot/#_O00308-mappedCitation-31924572 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31924572 |
| http://purl.uniprot.org/uniprot/B4DIN7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31924572 |
| http://purl.uniprot.org/uniprot/B4DHF6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31924572 |
| http://purl.uniprot.org/uniprot/O00308 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31924572 |