Linked Life Data

8175801

Source:http://linkedlifedata.com/resource/pubmed/id/8175801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1994-6-9
pubmed:databankReference
pubmed:abstractText
Using transfection and gel retardation assays, we have characterized further the antioxidant response element (ARE) found in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene. The ARE core sequence (5'-GTGACAAAGC-3') is sufficient for transcriptional activation of the Ya subunit gene by metabolizable planar aromatic compounds, phenolic antioxidants, and hydrogen peroxide. When the ARE sequence is ligated to a chloramphenicol acetyltransferase reporter gene and transfected into HepG2 cells, chloramphenicol acetyltransferase activity is modestly inducible by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Since the ARE is responsive to TPA and shows some sequence similarity to an AP-1-binding site (Jun/Fos recognition motif), we have explored whether members of the Jun/Fos family of transcription factors might bind to the ARE. Using in vitro synthesized Jun and Fos, binding to the ARE could not be detected, whereas Jun/Fos binding to a classical AP-1-binding site, a TPA response element (TRE) from the human collagenase gene, could be demonstrated by gel retardation assays. If the 2 A nucleotides underlined in the ARE core sequence (5'-GTGACAAAGC-3') are changed to TC, the ARE sequence (ARE-TRE) becomes a high-affinity AP-1-binding site and retains xenobiotic inducibility. Removal of the -GC- dinucleotide at the 3'-end of the ARE or the ARE-TRE eliminates xenobiotic inducibility. However, the ARE-TRE construct without the -GC- dinucleotide is still a high-affinity AP-1 site and responsive to TPA. Taken together, our data suggest that the ARE is not a high-affinity binding site for the Jun/Fos heterodimer. Functionally, however, an AP-1-binding site can resemble an ARE in its response to various xenobiotics if a 3'-GC- dinucleotide is present.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13656-62
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:8175801-Animals, pubmed-meshheading:8175801-Antioxidants, pubmed-meshheading:8175801-Base Sequence, pubmed-meshheading:8175801-Enzyme Activation, pubmed-meshheading:8175801-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8175801-Glutathione Transferase, pubmed-meshheading:8175801-Humans, pubmed-meshheading:8175801-Liver, pubmed-meshheading:8175801-Molecular Sequence Data, pubmed-meshheading:8175801-Oligodeoxyribonucleotides, pubmed-meshheading:8175801-Proto-Oncogene Proteins c-fos, pubmed-meshheading:8175801-Proto-Oncogene Proteins c-jun, pubmed-meshheading:8175801-Rats, pubmed-meshheading:8175801-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:8175801-Tetradecanoylphorbol Acetate, pubmed-meshheading:8175801-Transcription, Genetic, pubmed-meshheading:8175801-Tumor Cells, Cultured
pubmed:year
1994
pubmed:articleTitle
Transcriptional regulation of a rat liver glutathione S-transferase Ya subunit gene. Analysis of the antioxidant response element and its activation by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.
pubmed:affiliation
Department of Molecular Biology, Merck Frosst Center for Therapeutic Research, Merck Frosst Canada Inc., Pointe Claire-Dorval, Quebec, Canada.
pubmed:publicationType
Journal Article