@article {Chen2057, author = {Lei-Chin Chen and Ben-Kuen Chen and Wen-Chang Chang}, title = {Activating Protein 1-Mediated Cyclooxygenase-2 Expression Is Independent of N-Terminal Phosphorylation of c-Jun}, volume = {67}, number = {6}, pages = {2057--2069}, year = {2005}, doi = {10.1124/mol.104.010900}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/67/6/2057}, eprint = {https://molpharm.aspetjournals.org/content/67/6/2057.full.pdf}, journal = {Molecular Pharmacology} }