Genomic imprinting of p57KIP2, a cyclin–dependent kinase inhibitor, in mouse

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Abstract

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation1,2. The gene encoding human p57KIP is located on chromosome 11 p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it a tumour suppressor candidate. Several types of childhood tumours including Wilm's tumour, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting3–8 plays an important part9–12. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting13. Here, as a first step towards elucidating the genesis of human cancers in this region, we showed that a mouse homologue of p57KIP2 is genomically imprinted. The paternally inherited allele is transcriptionally repressed and methylated. This murine gene maps to the distal region of chromosome7, within acluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14–18).

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Hatada, I., Mukai, T. Genomic imprinting of p57KIP2, a cyclin–dependent kinase inhibitor, in mouse. Nat Genet 11, 204–206 (1995) doi:10.1038/ng1095-204

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