Characterization of the human p57(KIP2) gene: Alternative splicing, insertion deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis

We have isolated human cDNA and genomic clones of a gene termed p57(KIP2), which is related to the p21(WAF1) and p27(KIP1) genes that encode inducible inhibitors of cyclin-dependent kinase activity. The p57 gene contains three GC-rich introns of 166 bp, 566 bp, and 83 bp, and two of the four exons correspond to coding regions. Alternative splicing generates the heterogeneity in the translational initiations. As this gene has been localized to chromosomal band 11p15.5, a region thought to be the location of a tumor suppressor gene(s) for carcinomas of the breast, bladder, and liver, we have examined a large number of tumors for genetic alterations of p57. Although no somatic mutation has been detected, we have found several normal variations in this gene, including four types of 12-bp in-frame deletions in the proline/alanine repeating domain, in which nearly 40 motifs, viz., 5'CCGGCC-3', are tandemly repeated.