Source:http://linkedlifedata.com/resource/pubmed/id/14678988
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
23
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pubmed:dateCreated |
2003-12-17
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pubmed:abstractText |
EBV latent infection is associated with the development of lymphoid and epithelial malignancies such as nasopharyngeal carcinoma (NPC). The EBV latent membrane protein 1 (LMP1) acts as a constitutively active tumor necrosis factor receptor and activates cellular signaling pathways such as c-Jun-NH(2)-terminal kinase, cdc42, Akt, and nuclear factor (NF)-kappaB. In epithelial cells, two regions of LMP1 induce specific forms of NF-kappaB. COOH-terminal activating region 2 only activates p52/p65 dimers, whereas COOH-terminal activating region 1 activates p50/p50, p50/p52, and p52/p65 dimers and also uniquely up-regulates the epidermal growth factor receptor (EGFR) at the mRNA level. Deregulation of specific NF-kappaB members is associated with the development of many cancers. In this study, the status of NF-kappaB activation was investigated in NPC to determine which NF-kappaB dimers may contribute to the development of NPC. Electrophoretic mobility shift assay, immunoblot, ELISA, and immunohistochemistry data demonstrate that in NPC, NF-kappaB p50 homodimers are specifically activated, and this activation is not dependent on LMP1 expression. Coimmunoprecipitation assays indicate that homodimers are bound to the transcriptional coactivator Bcl-3, and chromatin immunoprecipitation indicates that this complex is bound to NF-kappaB consensus motifs within the egfr promoter in NPC. The discrete yet striking NF-kappaB p50 activation in NPC suggests that p50/p50 homodimers may be important factors in the development of NPC and may contribute to oncogenesis through transcriptional up-regulation of target genes through their interaction with Bcl-3.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/EBV-associated membrane antigen...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein bcl-3
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
63
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8293-301
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14678988-Cell Nucleus,
pubmed-meshheading:14678988-Genes, erbB-1,
pubmed-meshheading:14678988-Humans,
pubmed-meshheading:14678988-NF-kappa B,
pubmed-meshheading:14678988-NF-kappa B p50 Subunit,
pubmed-meshheading:14678988-Nasopharyngeal Neoplasms,
pubmed-meshheading:14678988-Precipitin Tests,
pubmed-meshheading:14678988-Promoter Regions, Genetic,
pubmed-meshheading:14678988-Proto-Oncogene Proteins,
pubmed-meshheading:14678988-RNA, Messenger,
pubmed-meshheading:14678988-Transcription Factors,
pubmed-meshheading:14678988-Transcriptional Activation,
pubmed-meshheading:14678988-Viral Matrix Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma.
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pubmed:affiliation |
Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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