Promoter region of the mouse cyclin-dependent kinase 5-encoding gene

Abstract

While cyclin-dependent kinases, such as CDC2 and CDK2, are key regulators of cell-cycle progression, cyclin-dependent kinase 5 (CDK5) is highly expressed in mature neurons with no evident cell-cycle regulation. The 5′-region of the mouse CDK5 gene was isolated and sequenced. The isolated clone included exons 1 through 7. The 5′-flanking region has a high G+C content. There is no TATA box around the transcriptional start points ( tsp), as determined by primer extension analysis. One CCAAT box, one AP-1-binding site, two AP-2-binding sites, and one cAMP-responsive element are located upstream from the tsp. Promoter/ cat fusion assays showed that the 5.8-kb fragment of this 5′-flanking sequence possessed the promoter activities expressing cat in rat PC12 pheochromocytoma cells. The effect of deletions of the promoter suggested the presence of two negative control elements located from −2.9 kb to −546 bp, and from −212 to −155 upstream from the 5′ end of the tsp. Two positive elements from bp −300 to −212 and from −155 to −41 were also detected. In the element from bp −300 to −212, there was a putative NF-IL6-binding sequence. Thus, the CDK5 promoter region contains multiple positive and negative cis-acting regulatory elements, an arrangement which suggests that the regulation of transcription of CDK5 is under complex control.