| http://purl.uniprot.org/citations/29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29795446 | http://www.w3.org/2000/01/rdf-schema#comment | "The inflammatory cytokine TNFα plays a crucial role in the pathology of many inflammatory and infectious diseases. However, the mechanism underlying TNFα cytotoxicity in these diseases is incompletely understood. Here we report that the pro-apoptotic BCL-2 family member BAD mediates TNFα cytotoxicity despite concurrent activation of IKK and NF-κB in vitro by inducing apoptosis in cultured cells and in vivo by eliciting tissue damage of multiple organs and contributing to mortality in septic shock. At high doses, TNFα significantly inactivates RhoA through activation of the Src-p190GAP pathway, resulting in massive actin stress fiber destabilization, followed by substantial BAD release from the cytoskeleton to the cytosol. Under this condition, activated IKK fails to phosphorylate all cytosolic BAD, allowing translocation of non-phosphorylated BAD to mitochondria to trigger apoptosis. Polymicrobial infection utilizes the same mechanism as high-dose TNFα to elicit apoptosis-associated tissue damage of multiple organs. Consequently, loss of Bad or elimination of BAD pro-apoptotic activity protects mice from tissue damage of multiple organs and reduces mortality rates. Our results support a model in which BAD mediates TNFα cytotoxicity despite concurrent activation of the IKK-NF-κB pathway in cultured mammalian cells and in septic shock."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41422-018-0041-7"xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Sun B."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Yuan X."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Zhao Y."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Yan J."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Xiang J."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/author | "Lin A."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/name | "Cell Res"xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/pages | "701-718"xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/title | "The BH3-only protein BAD mediates TNFalpha cytotoxicity despite concurrent activation of IKK and NF-kappaB in septic shock."xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://purl.uniprot.org/core/volume | "28"xsd:string |
| http://purl.uniprot.org/citations/29795446 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29795446 |
| http://purl.uniprot.org/citations/29795446 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29795446 |
| http://purl.uniprot.org/uniprot/#_D3YXL4-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_A0A494BBC4-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_D3YZR8-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_F6R6K0-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_F6S493-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_F7A4X5-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_F7ABX5-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |
| http://purl.uniprot.org/uniprot/#_P25118-mappedCitation-29795446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29795446 |