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Research ArticleArticle

Activating Protein 1-Mediated Cyclooxygenase-2 Expression Is Independent of N-Terminal Phosphorylation of c-Jun

Lei-Chin Chen, Ben-Kuen Chen and Wen-Chang Chang
Molecular Pharmacology June 2005, 67 (6) 2057-2069; DOI: https://doi.org/10.1124/mol.104.010900
Lei-Chin Chen
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Ben-Kuen Chen
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Wen-Chang Chang
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Abstract

Transcriptional activation of the cyclooxygenase (COX)-2 gene is responsible for high level of prostaglandin production during inflammation and carcinogenesis. We found previously that c-Jun induction plays a crucial role in epidermal growth factor (EGF)-induced gene expression of COX-2. In this study, the functional role of c-Jun in EGF-induced transcriptional activation of COX-2 in A431 cells was investigated. We found that overexpression of c-Jun N-terminal phosphorylation site mutants had similar stimulatory effects on COX-2 promoter activity and protein expression as c-Jun wild type. TAM-67, a mutant of c-Jun that lacks the N-terminal transactivation domain of c-Jun, also enhanced COX-2 promoter activity and protein expression in cells treated with EGF. In vitro DNA affinity precipitation and reporter assays revealed that regulation of c-Jun C terminus by EGF enhanced c-Jun binding to COX-2 promoter and induced COX-2 expression. Furthermore, we demonstrated that c-Fos, which provides transactivation function in Jun/Fos heterodimer, was required for EGF-induced expression of COX-2. These results indicated that c-Jun N-terminal phosphorylation was not required for EGF-induced expression of COX-2. c-Jun, which could recruit other transcription factors such as c-Fos, was required for EGF-induced expression of COX-2 in A431 cells.

  • Received January 4, 2005.
  • Accepted March 15, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (6)
Molecular Pharmacology
Vol. 67, Issue 6
1 Jun 2005
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Research ArticleArticle

Activating Protein 1-Mediated Cyclooxygenase-2 Expression Is Independent of N-Terminal Phosphorylation of c-Jun

Lei-Chin Chen, Ben-Kuen Chen and Wen-Chang Chang
Molecular Pharmacology June 1, 2005, 67 (6) 2057-2069; DOI: https://doi.org/10.1124/mol.104.010900

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Research ArticleArticle

Activating Protein 1-Mediated Cyclooxygenase-2 Expression Is Independent of N-Terminal Phosphorylation of c-Jun

Lei-Chin Chen, Ben-Kuen Chen and Wen-Chang Chang
Molecular Pharmacology June 1, 2005, 67 (6) 2057-2069; DOI: https://doi.org/10.1124/mol.104.010900
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