Promoter analysis of the human p44 mitogen-activated protein kinase gene (MAPK3): transcriptional repression under nonproliferating conditions

Abstract We have analyzed the promoter of the human p44mapk gene (approved symbol MAPK3 ) and found that the elements responsible for basal transcriptional activity are located within 200 bp upstream of the initiation codon in the 5′ UTR. This sequence has a high G/C content (80.5%), with four Sp1 sites and an E box as the most relevant motifs. Site-directed mutagenesis, EMSA, and DNase I footprinting experiments demonstrate that all these elements are essential to achieve a significant level of transcription. We also report that the promoter activity is strongly repressed when the cells are brought under growth arrest conditions, such as confluence or serum withdrawal. This finding suggests that in the process of cell proliferation, together with the modulation of p44mapk kinase activity by the rapid mechanism of phosphorylation/dephosphorylation, a long-term more adaptive regulation, based on gene transcription, might also be important.