Structure and expression of the human p58clk-1 protein kinase chromosomal gene.

A cDNA corresponding to a 58-kDa cell division control-related protein kinase, p58clk-1, has previously been isolated, sequenced, and assigned to human chromosome 1p36. Aberrant expression of this protein kinase negatively regulates normal cellular growth. The p58clk-1 protein contains a central domain of 299 amino acids that is 46% identical to human p34cdc2, the master mitotic protein kinase. Deletion of 1p36 has been correlated to numerous tumors, and this chromosome region has been suggested to harbor a putative tumor suppressor gene on the basis of the growth characteristics of these tumors. In this report we detail the complete structure of the p58clk-1 chromosomal gene, including its putative promoter region, transcriptional start sites, exonic sequences, and intron/exon boundary sequences. The gene is 10 kb in size and contains 12 exons and 11 introns. Interestingly, the rather large 2.0-kb 3' untranslated region is interrupted by an intron that separates a region containing numerous AUUUA destabilization motifs from the coding region. Furthermore, we detail the expression of this gene in normal human tissues as well as several human tumor cell samples and lines. The origin of multiple human transcripts from the same chromosomal gene, and the possible differential stability of these various transcripts, is discussed with regard to the transcriptional and post-transcriptional regulation of this gene. This is the first report of the chromosomal gene structure of a member of the p34cdc2 supergene family.