Functional analysis of the p57(KIP2) gene mutation in Beckwith-Wiedemann syndrome

Zahurul A. Bhuiyan, Hitomi Yatsuki, Toshiyuki Sasaguri, Keiichiro Joh, Hidenobu Soejima, Xike Zhu, Izuho Hatada, Hiroko Morisaki, Takayuki Morisaki, Tsunehiro Mukai

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


p57(KIP2) is a potent tight-binding inhibitor of several G1 cyclin/cyclin-dependent kinase (Cdk) complexes, and is a negative regulator of cell proliferation. The gene encoding p57(KIP2) is located at 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS). Previously we demonstrated that p57(KIP2) is imprinted and only the maternal allele is expressed in both mice and humans. We also showed mutations found in p57(KIP2) in patients with BWS that were transmitted from the patients' carrier mothers, indicating that the expressed maternal allele was mutant and that the repressed paternal allele was normal. In the study reported here, we performed functional analysis of the two mutated p57(KIP2) genes. We showed that the nonsense mutation found in the Cdk inhibitory domain in a BWS patient rendered the protein inactive with consequent complete loss of its role as a cell cycle inhibitor and of its nuclear localization. We also showed that the mutation in the QT domain, although completely retaining its cell cycle regulatory activity, lacked nuclear localization and was thus prevented from performing its role as an active cell cycle inhibitor. Consequently, no active p57(KIP2) would have existed, which might have caused the disorders in BWS patients.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalHuman Genetics
Issue number3
Publication statusPublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Functional analysis of the p57(KIP2) gene mutation in Beckwith-Wiedemann syndrome'. Together they form a unique fingerprint.

Cite this