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

Nat Genet. 1995 Oct;11(2):204-6. doi: 10.1038/ng1095-204.

Abstract

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (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 imprinting plays an important part. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting. 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 chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14-18).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics
  • Animals
  • Base Sequence
  • Beckwith-Wiedemann Syndrome / genetics
  • Child
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 11*
  • Crosses, Genetic
  • Cyclin-Dependent Kinase Inhibitor p57
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • DNA Primers
  • Enzyme Inhibitors
  • Female
  • Genes, Tumor Suppressor
  • Genetic Carrier Screening
  • Humans
  • Kidney Neoplasms / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Muridae
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction
  • Recombination, Genetic
  • Rhabdomyosarcoma / genetics
  • Wilms Tumor / genetics

Substances

  • CDKN1C protein, human
  • Cdkn1c protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p57
  • DNA Primers
  • Enzyme Inhibitors
  • Nuclear Proteins
  • Cyclin-Dependent Kinases