| http://purl.uniprot.org/citations/16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16953224 | http://www.w3.org/2000/01/rdf-schema#comment | "Constitutively activated nuclear factor-kappaB (NF-kappaB) has been associated with a variety of aggressive tumor types, including head and neck squamous cell carcinoma (HNSCC); however, the mechanism of its activation is not fully understood. Therefore, we investigated the molecular pathway that mediates constitutive activation of NF-kappaB in a series of HNSCC cell lines. We confirmed that NF-kappaB was constitutively active in all HNSCC cell lines (FaDu, LICR-LON-HN5 and SCC4) examined as indicated by DNA binding, immunocytochemical localization of p65, by NF-kappaB-dependent reporter gene expression and its inhibition by dominant-negative (DN)-inhibitory subunit of NF-kappaB (IkappaBalpha), the natural inhibitor of NF-kappaB. Constitutive NF-kappaB activation in HNSCC was found to be due to constitutive activation of IkappaBalpha kinase (IKK); and this correlated with constitutive expression of phosphorylated forms of IkappaBalpha and p65 proteins. All HNSCC showed the expression of p50, p52, p100 and receptor-interacting protein; all linked with NF-kappaB activation. The expression of constitutively active NF-kappaB in HNSCC is mediated through the tumor necrosis factor (TNF) signaling pathway, as NF-kappaB reporter activity was inhibited by DN-TNF receptor-associated death domain (TRADD), DN-TNF receptor-associated factor (TRAF)2, DN-receptor-interacting protein (RIP), DN-transforming growth factor-beta-activated kinase 1 (TAK1), DN-kappa-Ras, DN-AKT and DN-IKK but not by DN-TRAF5 or DN-TRAF6. Constitutive NF-kappaB activation was also associated with the autocrine expression of TNF, TNF receptors and receptor-activator of NF-kappaB and its ligand in HNSCC cells but not interleukin (IL)-1beta. All HNSCC cell lines expressed IL-6, a NF-kappaB-regulated gene product. Furthermore, treatment of HNSCC cells with anti-TNF antibody downregulated constitutively active NF-kappaB, and this was associated with inhibition of IL-6 expression and cell proliferation. Our results clearly demonstrate that constitutive activation of NF-kappaB is mediated through the TRADD-TRAF2-RIP-TAK1-IKK pathway, making TNF a novel target in the treatment of head and neck cancer."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.onc.1209945"xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Ichikawa H."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Darnay B.G."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Aggarwal B.B."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Lin X.L."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Chaturvedi M.M."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Myers J.N."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/author | "Jackson-Bernitsas D.G."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/pages | "1385-1397"xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/title | "Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma."xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://purl.uniprot.org/core/volume | "26"xsd:string |
| http://purl.uniprot.org/citations/16953224 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16953224 |
| http://purl.uniprot.org/citations/16953224 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16953224 |
| http://purl.uniprot.org/uniprot/#_Q15628-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_P21580-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_P01375-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_Q12933-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_Q13107-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_Q13489-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |
| http://purl.uniprot.org/uniprot/#_Q13490-mappedCitation-16953224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16953224 |