The p34Cdc2-associated protein kinase family (PITSLRE kinase) is produced by three repeated and tandemly linked genes on human chromosome 1p36.3 through alternative splicing and promoter utilization. This gene is often deleted in the late stages of tumorigenesis. PITSLRE mRNA, protein and enzyme activity are induced during Fas receptor and glucocorticoid-mediated human T cell apoptosis. Several PITSLRE isoforms are specific targets for proteolysis during apoptosis and can produce 50 kDa isoforms with enzymatic activity. Inhibition of this protease activity prevents PITSLRE processing and enzyme activation and apoptosis. Therefore, PITSLRE kinase can be an integral downstream component of the apoptotic signal transduction pathway. In addition, the PITSLRE gene and its products have undergone physical changes in human neuroblastoma tumors, suggesting that they may be tumor suppressors.
PITSLRE serine/threonine protein kinase CDC2L1 is an enzyme encoded by the CDC2L1 gene in humans, which encodes a member of the p34Cdc2 protein kinase family. It is known that members of the p34Cdc2 kinase family are essential for eukaryotic cell cycle control. This gene is very close to CDC2L2. CDC2L2 is almost the same gene in the same chromosomal region. The gene locus CDC2L2 and the metalloproteinase MMP21/22, which consist of the gene, consist of two identical tandem-linked genomic regions, which are considered to be part of a larger region that has been replicated. This gene and CDC2L2 show frequent deletions or changes in neuroblastomas with the amplified MYCN gene. The gene encodes a protein kinase that can be cleaved by caspase and has been shown to play a role in apoptosis. Several alternative splicing variants of this gene have been reported.
The product of the Cdc2L gene encodes almost the same protein kinase, PITSLRE kinase, whose function may be related to the regulation of transcription / splicing and apoptosis signals. These genes are deleted/metastasis in neuroblastomas with a MYCN gene amplification, a subset of malignant melanomas, and the newly described deletion syndrome. Here we report that the p36.3 region of human chromosome 1 consists of two identical genomic regions, each of which contains a Cdc2L gene that is linked to the metalloproteinase (MMP) gene in a tail-to-tail configuration. This repeated genomic region is also closely linked to D1Z2, a genetic marker that contains a highly polymorphic VNTR (variable number of tandem repeats) and consists of an unusual 40 bp repeat. It is worth noting that the introns and exons of Cdc2L1 and Cdc2L2, and their flanking regions are basically the same. Among the 773-786 amino acids designated by the various products of the Cdc2L gene, a total of 15 amino acid differences, 12 non-conservative amino acids, and 3 conservative amino acids can be found. Two independent promoters/5 'untranslated (UT) regions, CpG1 and CpG2, are identical to the previously reported methylated genomic CpG sequences and can be used to express> 20 different Cdc2L transcripts from two genes. The expression of CpG2 transcripts from Cdc2L1 and Cdc2L2 is tissue/cell line specific. CpG1 transcripts are commonly expressed in these two genes, and may be biased against CpG1 Cdc2L1 mRNA expression in some hematopoietic cells.