Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15

Shuhei Matsuoka, Jeffrey S. Thompson, Michael C. Edwards, Janet M. Barletta, Paul Grundy, Linda M. Kalikin, J. Wade Harper, Stephen J. Elledge, Andrew P. Feinberg

Research output: Contribution to journalArticlepeer-review

Abstract

Parental origin-specific alterations of chromosome 11p15 in human cancer suggest the involvement of one or more maternally expressed imprinted genes involved in embryonal tumor suppression and the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). The gene encoding cyclin-dependent kinase inhibitor p57KIP2, whose overexprcssion causes G1 phase arrest, was recently cloned and mapped to this band. We find that the p57KIP2 gene is imprinted, with preferential expression of the maternal allele. However, the imprint is not absolute, as the paternal allele is also expressed at low levels in most tissues, and at levels comparable to the maternal allele in fetal brain and some embryonal tumors. The biochemical function, chromosomal location, and imprinting of the p57KIP2 gene match the properties predicted for a tumor suppressor gene at 11p15.5. However, as the p57KIP2 gene is 500 kb centromeric to the gene encoding insulin-like growth factor 2, it is likely to be part of a large domain containing other imprinted genes. Thus, loss of heterozygosity or loss of imprinting might simultaneously affect several genes at this locus that together contribute to tumor and/or growth-suppressing functions that are disrupted in BWS and embryonal tumors.

Original languageEnglish (US)
Pages (from-to)3026-3030
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number7
DOIs
StatePublished - Apr 2 1996

ASJC Scopus subject areas

  • General

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