CHARACTERIZATION OF THE HUMAN CYCLIN-DEPENDENT KINASE-2 GENE - PROMOTER ANALYSIS AND GENE STRUCTURE

Cyclin-dependent kinase 2 is a serine/threonine protein kinase essenti al for progression of the mammalian cell cycle from G(1) to S phase, C DK2 mRNA has been shown to be induced by serum in several cultured cel l types. Therefore, we set out to identify elements that regulate the transcription of the human CDK2 gene and to characterize its structure . This paper describes the cloning of a similar to 2.4-kilobase pair g enomic DNA fragment from the upstream region of the human CDK2 gene, T his fragment contains five transcription initiation sites within a 72- nucleotide stretch, A 200-base pair sub-fragment that confers 70% of m aximal basal promoter activity was shown to contain two synergisticall y acting Sp1 sites. However, a much larger DNA fragment containing sim ilar to 1.7 kilobase pairs of upstream sequence is required for induct ion of promoter activity following serum stimulation. The intron exon boundaries of seven exons in this gene were also identified, and this information will be useful for analyzing genomic abnormalities associa ted with CDK2.