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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1998-2-23
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pubmed:databankReference | |
pubmed:abstractText |
A novel cDNA was partially isolated from a HepG2 cell expression library by screening with the promoter-linked coupling element (PCE), a site from the alpha-fetoprotein (AFP) gene promoter. The remainder of the cDNA was cloned from fetal liver RNA using random amplification of cDNA ends. The cDNA encodes a 239-amino acid peptide with domains closely related to the Drosophila factor nk-2. The new factor is the eighth vertebrate factor related to nk-2, hence nkx-2.8. Northern blot and reverse transcriptase polymerase chain reaction analysis demonstrated mRNA in HepG2, two other AFP-expressing human cell lines, and human fetal liver. Transcripts were not detected in adult liver. Cell-free translation produced DNA binding activity that gel shifted a PCE oligonucleotide. Cotransfection of nkx-2.8 expression and PCE reporter plasmids into HeLa cells demonstrated transcriptional activation; NH2-terminal deletion eliminated this activity. Cotransfection into AFP-producing hepatocytic cells repressed AFP reporter expression, suggesting that endogenous activity was already present in these cells. In contrast, cotransfection into an AFP-negative hepatocytic line produced moderate activation of the AFP gene. The cardiac developmental factor nkx-2.5 could substitute for nkx-2.8 in all transfection assays, whereas another related factor, thyroid transcription factor 1, showed a more limited range of substitution. Although the studies have yet to establish definitively that nkx-2.8 is the AFP gene regulator PCF, the two factors share a common DNA binding site, gel shift behavior, migration on SDS-acrylamide gels, and cellular distribution. Moreover, the nk-2-related genes are developmental regulators, and nkx-2.8 is the first such factor associated with liver development.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
|
pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
|
pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2917-25
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9446603-Amino Acid Sequence,
pubmed-meshheading:9446603-Base Sequence,
pubmed-meshheading:9446603-Binding Sites,
pubmed-meshheading:9446603-Carcinoma, Embryonal,
pubmed-meshheading:9446603-Carcinoma, Hepatocellular,
pubmed-meshheading:9446603-Cloning, Molecular,
pubmed-meshheading:9446603-Gene Expression Regulation, Developmental,
pubmed-meshheading:9446603-Humans,
pubmed-meshheading:9446603-Liver,
pubmed-meshheading:9446603-Liver Neoplasms,
pubmed-meshheading:9446603-Molecular Sequence Data,
pubmed-meshheading:9446603-Neoplasm Proteins,
pubmed-meshheading:9446603-Promoter Regions, Genetic,
pubmed-meshheading:9446603-Sequence Homology, Amino Acid,
pubmed-meshheading:9446603-Transcription Factors,
pubmed-meshheading:9446603-alpha-Fetoproteins
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pubmed:year |
1998
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pubmed:articleTitle |
A novel nk-2-related transcription factor associated with human fetal liver and hepatocellular carcinoma.
|
pubmed:affiliation |
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|