FIGURE 7 .

A schematic model depicting the potential preventative effects of RA against AP-1–dependent activation of COX-2 expression. Under the current model, several stimuli, including TPA, may activate signaling cascades that lead to the subsequent activation of mitogen-activated protein kinase pathways, including the ERK1/2. The ERK1/2 pathway contributes to the recruitment of members of the AP-1 factor, which comprises members of the Jun and Fos family of transcription factors, to the COX-2 promoter. RA may exert preventative effects against the induction of COX-2 transcription by antagonizing the activation of ERK1/2 and the recruitment of AP-1 factors to the CRE harbored in the proximal COX-2 promoter. Arrows indicate activation and the bar indicates repression by RA. Thr-202 and Tyr-204 indicate phosphorylation sites on ERK1/2. The +1 indicates the initiation of transcription of the COX-2 gene.