Activation of AP-1 by okadaic acid in mouse keratinocytes associated with hyperphosphorylation of c-jun

J Peng; G T Bowden; F E Domann

doi:10.1002/(SICI)1098-2744(199701)18:1<37::AID-MC5>3.0.CO;2-O

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Activation of AP-1 by okadaic acid in mouse keratinocytes associated with hyperphosphorylation of c-jun

Journal article

Peer reviewed

Activation of AP-1 by okadaic acid in mouse keratinocytes associated with hyperphosphorylation of c-jun

J Peng, G T Bowden and F E Domann

Molecular carcinogenesis, Vol.18(1), pp.37-43

01/1997

DOI: 10.1002/(SICI)1098-2744(199701)18:1<37::AID-MC5>3.0.CO;2-O

PMID: 9022811

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Abstract

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, is also a potent mouse skin tumor promoter. The effects of OA on regulation of c-jun/activator protein-1 (AP-1) transcriptional activation were investigated in mouse keratinocytes. AP-1 DNA binding to the jun 12-O-tetradecanoylphorbol-13-acetate-response element (TGACATCA) as determined by gel shift analysis was strongly induced by OA (100 ng/mL) at 6 and 12 h. Preincubation of nuclear extracts with anti-c-jun antibody demonstrated that c-jun was a major component of the DNA-bound AP-1 complex induced by OA in 308 cells. Transfection of a c-jun promoter-reporter construct demonstrated that AP-1 transactivation was induced by OA. The mRNA level of the c-jun proto-oncogene was dramatically increased by 6 and 12 h of OA treatment. Furthermore, a significant induction of c-jun protein was stimulated by 6 and 12 h of OA treatment. Upon further analysis, it was found that OA induced a significant accumulation of Ser 73-phosphorylated c-jun protein in 308 cells. In summary, our data suggest that skin tumor promotion by OA is due at least in part to increased AP-1 DNA binding and transactivation mediated by c-jun hyperphosphorylation.

Phosphorylation

Cell Line

Okadaic Acid - pharmacology

Promoter Regions, Genetic

Proto-Oncogene Proteins c-jun - genetics

Transcriptional Activation - drug effects

Enzyme Inhibitors - pharmacology

DNA - metabolism

Transcription Factor AP-1 - metabolism

RNA, Messenger - biosynthesis

Animals

Carcinogens - pharmacology

Keratinocytes - drug effects

Keratinocytes - metabolism

Proto-Oncogene Proteins c-jun - metabolism

Protein Binding - drug effects

Mice

Details

Title: Subtitle: Activation of AP-1 by okadaic acid in mouse keratinocytes associated with hyperphosphorylation of c-jun
Creators: J Peng - Division of Radiation Oncology, University of Iowa, Iowa City 52242, USA
G T Bowden
F E Domann
Resource Type: Journal article
Publication Details: Molecular carcinogenesis, Vol.18(1), pp.37-43
Publisher: United States
DOI: 10.1002/(SICI)1098-2744(199701)18:1<37::AID-MC5>3.0.CO;2-O
PMID: 9022811
ISSN: 0899-1987
eISSN: 1098-2744
Grant note: CA40584 / NCI NIH HHS
Language: English
Date published: 01/1997
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984046827502771

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