p57Kip2 (cdkn1c): Sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas

Tamara Potikha, Sameer Kassem, Esther P. Haber, Ilana Ariel, Benjamin Glaser

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The cyclin-dependent kinase (CDK) inhibitor p57Kip2 (CDKN1C) is a negative regulator of cell proliferation, binding to a variety of cyclin-CDK complexes and inhibiting their kinase activities in vitro. The p57 Kip2 gene is imprinted and the maternal allele is expressed in terminally differentiated cells, including human β-cells. Somatic loss of p57Kip2 expression is associated with increased β-cell proliferation in the focal form of Hyperinsulinism of Infancy. We cloned and sequenced the rat ortholog of p57Kip2, and demonstrate that it is highly homologous to the mouse gene. However, the human and rodent genes are quite divergent. Despite having highly homologous C- and N-terminal domains, the mid-portion of the human gene is entirely different from that of its rodent counterparts. Expression of p57Kip2 was evaluated during fetal and postnatal development, and a highly cell-specific, temporal and spatial expression profile was found. In contrast to other tissues, the expression pattern in rat pancreas was entirely opposite from that previously reported in man, with high levels of expression in rodent exocrine cells, but no expression in β-cells during any stage of development. These findings demonstrate that p57Kip2 expression is highly regulated. In the pancreas, the functional significance of this gene appears to be quite different in humans when compared with rodents, suggesting that a better understanding of the function of this protein may provide new insights into the mechanisms involved in the control of human β-cell mass.

Original languageEnglish
Pages (from-to)364-375
Number of pages12
JournalLaboratory Investigation
Issue number3
StatePublished - 1 Mar 2005
Externally publishedYes


  • Alternative splice
  • CDKN1C
  • Cell cycle
  • Diabetes
  • Islet transplantation
  • Pancreas regeneration
  • p57
  • β-cell
  • β-cell proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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