Document Detail


Activating protein 1-mediated cyclooxygenase-2 expression is independent of N-terminal phosphorylation of c-Jun.
MedLine Citation:
PMID:  15772294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lei-Chin Chen; Ben-Kuen Chen; Wen-Chang Chang
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-03-16
Journal Detail:
Title:  Molecular pharmacology     Volume:  67     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-17     Completed Date:  2005-07-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2057-69     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, National Cheng-Kung University, No.1 Ta-Hsueh Road, Tainan 701, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cyclooxygenase 2
Gene Expression Regulation, Enzymologic / physiology*
Humans
Membrane Proteins
Peptide Fragments / metabolism*
Phosphorylation
Prostaglandin-Endoperoxide Synthases / biosynthesis*,  genetics
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Transcription Factor AP-1 / biosynthesis*,  genetics
Transcriptional Activation / physiology
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Peptide Fragments; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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