| http://purl.uniprot.org/citations/23209320 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23209320 | http://www.w3.org/2000/01/rdf-schema#comment | "A deeper understanding of the mechanisms that control responses to inflammation is critical to the development of effective therapies. We sought to define the most proximal regulators of the Cullin (Cul)-RING ligases, which play a central role in the stabilization of NF-κB and hypoxia-inducible factor (HIF). In these studies, we identify the human deneddylase-1 (SENP8) as a key regulator of Cul neddylation response in vitro and in vivo. Using human microvascular endothelial cells (HMECs), we examined inflammatory responses to LPS or TNF-α by assessing Cul neddylation status, NF-κB and HIF-1α stabilization, and inflammatory cytokine secretion. HMECs with an intact neddylation pathway showed a time-dependent induction of Cul-1 neddylation, nuclear translocation of NF-κB, stabilization of HIF-1α, and increased NF-κB/HIF-α promoter activity in response to LPS. HMECs lacking SENP8 were unable to neddylate Cul-1 and subsequently were unable to activate NF-κB or HIF-1α. Pharmacological targeting of neddylation (MLN4924) significantly abrogated NF-κB responses, induced HIF-1α promoter activity, and reduced secretion of TNF-α-elicited proinflammatory cytokines. MLN4924 stabilized HIF and abrogated proinflammatory responses while maintaining anti-inflammatory IL-10 responses in vivo following LPS administration. These studies identify SENP8 as a proximal regulator of Cul neddylation and provide an important role for SENP8 in fine-tuning the inflammatory response. Moreover, our findings provide feasibility for therapeutic targeting of the Culs during inflammation."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1202041"xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Campbell E.L."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Colgan S.P."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Kelly C.J."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Kominsky D.J."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Glover L.E."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Bowers B.E."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Ehrentraut S.F."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/author | "Bayless A.J."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/pages | "392-400"xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/title | "Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response."xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://purl.uniprot.org/core/volume | "190"xsd:string |
| http://purl.uniprot.org/citations/23209320 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23209320 |
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