| http://purl.uniprot.org/citations/30224829 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30224829 | http://www.w3.org/2000/01/rdf-schema#comment | "Nur77 is a member of the NR4A subfamily of nuclear receptors and has been shown to regulate various biological processes such as apoptosis and inflammation. Here, we show that Nur77 ubiquitination is mediated by the tripartite motif 13 (Trim13), a RING-type E3 ubiquitin ligase. The interaction between Nur77 and Trim13 was confirmed by co-immunoprecipitation. Moreover, we found that Lys539 in Nur77 ubiquitination is targeted for Trim13, which leads to Nur77 degradation. The Trim13-mediated ubiquitination of Nur77 was optimal in the presence of the E2 enzyme UbcH5. Importantly, in addition to Trim13-mediated ubiquitination, the stability of Nur77 was also regulated by casein kinase 2α (CK2α). Pharmacological inhibition of CK2 markedly increased Nur77 levels, whereas overexpression of CK2α, but not its inactive mutant, dramatically decreased Nur77 levels by promoting Nur77 ubiquitination. CK2α phosphorylated Ser154 in Nur77 and thereby regulated Nur77 protein levels by promoting its ubiquitin-mediated degradation. Importantly, we also show that degradation of Nur77 is involved in TNFα-mediated IL-6 production via CK2α and Trim13. Taken together, these results suggest that the sequential phosphorylation and ubiquitination of Nur77 controls its degradation, and provide a therapeutic approach for regulating Nur77 activity through the CK2α-Trim13 axis as a mechanism to control the inflammatory response."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41598-018-32391-5"xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/author | "Huang B."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/author | "Chang H.W."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/author | "Baek S.H."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/author | "Pei H.Z."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/pages | "13895"xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/title | "The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2alpha."xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/30224829 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30224829 |
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