摘要
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.
| 原文 | English |
|---|---|
| 頁（從 - 到） | 2057-2069 |
| 頁數 | 13 |
| 期刊 | Molecular Pharmacology |
| 卷 | 67 |
| 發行號 | 6 |
| DOIs | |
| 出版狀態 | Published - 2005 六月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Pharmacology
引用此文
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Activating protein 1-mediated cyclooxygenase-2 expression is independent of N-terminal phosphorylation of c-Jun. / Chen, Lei Chin; Chen, Ben-Kuen; Chang, Wen Chang.
於: Molecular Pharmacology, 卷 67, 編號 6, 01.06.2005, p. 2057-2069.研究成果: Article
TY - JOUR
T1 - Activating protein 1-mediated cyclooxygenase-2 expression is independent of N-terminal phosphorylation of c-Jun
AU - Chen, Lei Chin
AU - Chen, Ben-Kuen
AU - Chang, Wen Chang
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
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U2 - 10.1124/mol.104.010900
DO - 10.1124/mol.104.010900
M3 - Article
C2 - 15772294
AN - SCOPUS:21744449641
VL - 67
SP - 2057
EP - 2069
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 6
ER -