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Genomic Organization of the Human p57Klp2 Gene and Its Analysis in the G401 Wilms' Tumor Assay1

The p57KII>2gene encodes an inhibitor of cyclin-depcndcnt kinasc ac tivity, which negatively regulates cell cycle progression. The human p57 gene is located in I Ipl5.5, a region of DNA frequently altered in neoplasia. We have isolated a human genomic clone and mapped the p57 gene to a 2.2-kb region between DIIS6-Ã•8 and Ãœ1IS679. Sequence analysis revealed that the coding DNA of the human p57 gene is divided by a 0.5-kb intron. A second intron was detected in the .V untranslated region, indicating that the human p57 gene contains at least three exons. Our previous work with somatic cell hybrids mapped a tumor suppressor gene for the (.4(11 Wilms' tumor cell line to a ~500-kb region of HplS.5 that includes p57. Northern blot analysis detected a O.S-kh p57 transcript in several of the (.4(11 hybrid lines. However, p57 expression did not correlate with tumor suppression. These results suggest that p57 is not responsible for the tumor suppression observed in our somatic cell hybrid assay.