Phorbol ester regulation of the human γ-glutamyltransferase gene promoter

In the present study the molecular mechanisms underlying tetradecanoylphorbol-13-acetate (TPA) mediated regulation of the human γ-glutamyltransferase (GGT) gene were examined. TPA challenge of HeLa cells resulted in an increase of GGT mRNA and enzyme activity. Deletion analysis of the promoter revea...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-01, Vol.313 (2), p.300-307
Main Authors: Daubeuf, Sandrine, Duvoix, Annelyse, Wellman-Rousseau, Maria, Diederich, Marc, Visvikis, Athanase
Format: Article
Language:English
Subjects:
Activating protein 1
Binding Sites
Biochemistry, Molecular Biology
Cell Line, Tumor
DNA-Binding Proteins - metabolism
Electrophoretic Mobility Shift Assay
Enhancer Elements, Genetic - genetics
Enzyme Induction - drug effects
gamma-Glutamyltransferase - genetics
gamma-Glutamyltransferase - metabolism
Gene Expression Regulation - drug effects
Genes, Reporter - genetics
HeLa Cells
Humans
Life Sciences
Luciferases - metabolism
Molecular biology
Promoter Regions, Genetic - drug effects
Protein Binding
Proto-Oncogene Proteins c-jun - metabolism
RNA, Messenger - biosynthesis
Tetradecanoylphorbol Acetate - pharmacology
TPA induction
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcriptional regulation
Transfection
γ-Glutamyltransferase
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Summary:In the present study the molecular mechanisms underlying tetradecanoylphorbol-13-acetate (TPA) mediated regulation of the human γ-glutamyltransferase (GGT) gene were examined. TPA challenge of HeLa cells resulted in an increase of GGT mRNA and enzyme activity. Deletion analysis of the promoter revealed that the −348 to +60 fragment was able to mediate TPA induced expression. Gel shift and supershift analyses showed that TPA treatment increased nuclear protein binding to a putative AP-1 site (−225 to −214) and that c-Jun was part of the complex. This AP-1 element, when cloned either in its native arrangement or as tandem repeat 5′ of the minimal thymidine kinase promoter, mediated a significant increase of luciferase activity after TPA treatment of transfected HeLa cells, while its mutated counterpart abolished the induction. The same AP-1 element was able to mediate TPA induced expression in HepG2 cells. Collectively these results indicate that like other GSH metabolising enzymes, GGT too is a target for AP-1 mediated regulation.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2003.11.121