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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
1992-10-7
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pubmed:databankReference |
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pubmed:abstractText |
A20 was first identified as a tumor necrosis factor (TNF) primary response transcript encoding a 790-amino acid protein with a unique zinc finger motif. Recently, A20 was shown to protect cells from TNF-induced cytotoxicity in a variety of cell lines. Nuclear run-on studies previously established that TNF activates A20 at the transcriptional level. To further characterize the mechanism by which TNF activates the A20 gene, we have cloned the A20 5'-flanking sequences and identified TNF-responsive elements within the promoter. The transcription initiation site was mapped by both primer extension and S1 nuclease protection experiments to a position 4.2 kilobases (kb) upstream of the initiator methionine; the first and second exon were separated by a 3.9-kb intron. Sequences upstream of the transcription start site were 76% GC-rich and contained six Sp1 binding sites and a TATA-like sequence at -29 but lacked a consensus CCAAT site. Transfection of Jurkat T-cells with an array of A20 promoter CAT constructs showed that two kappa B elements residing at -54 and -66 were required for induction by TNF. Supporting this notion, DNA electrophoretic mobility shift assays using nuclear extracts from unstimulated and TNF-stimulated Jurkat cells demonstrated kappa B-specific binding of a TNF-activated factor to an end-labeled probe containing the two A20 kappa B sequences. Finally, evidence obtained from cotransfection experiments showed that A20 negatively regulated its own expression.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17971-6
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:1381359-Amino Acid Sequence,
pubmed-meshheading:1381359-Base Sequence,
pubmed-meshheading:1381359-Cell Line,
pubmed-meshheading:1381359-Endothelium, Vascular,
pubmed-meshheading:1381359-Female,
pubmed-meshheading:1381359-Gene Expression Regulation,
pubmed-meshheading:1381359-Genomic Library,
pubmed-meshheading:1381359-Humans,
pubmed-meshheading:1381359-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:1381359-Molecular Sequence Data,
pubmed-meshheading:1381359-NF-kappa B,
pubmed-meshheading:1381359-Nuclear Proteins,
pubmed-meshheading:1381359-Oligodeoxyribonucleotides,
pubmed-meshheading:1381359-Placenta,
pubmed-meshheading:1381359-Plasmids,
pubmed-meshheading:1381359-Poly A,
pubmed-meshheading:1381359-Pregnancy,
pubmed-meshheading:1381359-Promoter Regions, Genetic,
pubmed-meshheading:1381359-Protein Biosynthesis,
pubmed-meshheading:1381359-Proteins,
pubmed-meshheading:1381359-RNA,
pubmed-meshheading:1381359-RNA, Messenger,
pubmed-meshheading:1381359-Restriction Mapping,
pubmed-meshheading:1381359-Transcription, Genetic,
pubmed-meshheading:1381359-Transfection,
pubmed-meshheading:1381359-Tumor Necrosis Factor-alpha,
pubmed-meshheading:1381359-Zinc Fingers
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pubmed:year |
1992
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pubmed:articleTitle |
Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements.
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pubmed:affiliation |
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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