| http://purl.uniprot.org/citations/24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24085292 | http://www.w3.org/2000/01/rdf-schema#comment | "Proteasome inhibitors (PIs) have been reported to induce apoptosis in many types of tumor. Their apoptotic activities have been suggested to be associated with the up-regulation of molecules implicated in pro-apoptotic cascades such as p53, p21(Waf1), and p27(Kip1). Moreover, the blocking of NF-κB nuclear translocation via the stabilization of IκB is an important mechanism of PI-induced apoptosis. However, we found that long-term incubation with PIs (PS-341 or MG132) increased NF-κB-regulated gene expression such as COX-2, cIAP2, XIAP, and IL-8 in a dose- and time-dependent manner, which was mediated by phosphorylation of IκBα and its subsequent degradation via the alternative route, lysosome. Overexpression of the IκBα superrepressor (IκBα-SR) blocked PI-induced NF-κB activation. Treatment with lysosomal inhibitors (ammonium chloride or chloroquine) or inhibitors of cathepsins (Z-FF-FMK or Z-FA-FMK) or knock-down of LC3B expression by siRNAs suppressed PI-induced IκBα degradation. Furthermore, we found that both IKK-dependent and IKK-independent pathways were required for PI-induced IκBα degradation. Pretreatment with IKKβ specific inhibitor, SC-514, partially suppressed IκBα degradation and IL-8 production by PIs. Blockade of IKK activity using insolubilization by heat shock (HS) and knock-down by siRNAs for IKKβ only delayed IκBα degradation up to 8 h after treatment with PIs. In addition, PIs induced Akt-dependent inactivation of GSK-3β. Inactive GSK-3β accelerated PI-induced IκBα degradation. Overexpression of active GSK-3β (S9A) or knock-down of GSK-3β delayed PI-induced IκBα degradation. Collectively, our data demonstrate that long-term incubation with PIs activates NF-κB, which is mediated by IκBα degradation via the lysosome in an IKK-dependent and IKK-independent manner."xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.480921"xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/author | "Lee K.H."xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/author | "Jeong J."xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/author | "Yoo C.G."xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/pages | "32777-32786"xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/title | "Long-term incubation with proteasome inhibitors (PIs) induces IkappaBalpha degradation via the lysosomal pathway in an IkappaB kinase (IKK)-dependent and IKK-independent manner."xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://purl.uniprot.org/core/volume | "288"xsd:string |
| http://purl.uniprot.org/citations/24085292 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24085292 |
| http://purl.uniprot.org/citations/24085292 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24085292 |
| http://purl.uniprot.org/uniprot/#_P25963-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/#_Q9UGJ4-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/#_Q9UGJ5-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/#_Q9UGJ6-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/#_Q9UGJ7-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/#_Q9UGJ8-mappedCitation-24085292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/Q9UGJ4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/Q9UGJ5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/Q9UGJ8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/Q9UGJ7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/P25963 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |
| http://purl.uniprot.org/uniprot/Q9UGJ6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24085292 |