| http://purl.uniprot.org/citations/25766331 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25766331 | http://www.w3.org/2000/01/rdf-schema#comment | "Recently, we reported that induction of the co-chaperone Bcl-2-associated athanogene 3 (BAG3) is critical for recovery of rhabdomyosarcoma (RMS) cells after proteotoxic stress upon inhibition of the two constitutive protein degradation pathways, that is, the ubiquitin-proteasome system by Bortezomib and the aggresome-autophagy system by histone deacetylase 6 (HDAC6) inhibitor ST80. In the present study, we investigated the molecular mechanisms mediating BAG3 induction under these conditions. Here, we identify nuclear factor-kappa B (NF-κB)-inducing kinase (NIK) as a key mediator of ST80/Bortezomib-stimulated NF-κB activation and transcriptional upregulation of BAG3. ST80/Bortezomib cotreatment upregulates mRNA and protein expression of NIK, which is accompanied by an initial increase in histone H3 acetylation. Importantly, NIK silencing by siRNA abolishes NF-κB activation and BAG3 induction by ST80/Bortezomib. Furthermore, ST80/Bortezomib cotreatment stimulates NF-κB transcriptional activity and upregulates NF-κB target genes. Genetic inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor (IκBα-SR) or by knockdown of p65 blocks the ST80/Bortezomib-stimulated upregulation of BAG3 mRNA and protein expression. Interestingly, inhibition of lysosomal activity by Bafilomycin A1 inhibits ST80/Bortezomib-stimulated IκBα degradation, NF-κB activation and BAG3 upregulation, indicating that IκBα is degraded via the lysosome in the presence of Bortezomib. Thus, by demonstrating a critical role of NIK in mediating NF-κB activation and BAG3 induction upon ST80/Bortezomib cotreatment, our study provides novel insights into mechanisms of resistance to proteotoxic stress in RMS."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.org/dc/terms/identifier | "doi:10.1038/cddis.2014.584"xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/author | "Jung M."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/author | "Fulda S."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/author | "Abhari B.A."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/author | "Rapino F."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/pages | "e1692"xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/title | "NIK is required for NF-kappaB-mediated induction of BAG3 upon inhibition of constitutive protein degradation pathways."xsd:string |
| http://purl.uniprot.org/citations/25766331 | http://purl.uniprot.org/core/volume | "6"xsd:string |
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