The cyclin-dependent kinase inhibitor p27(Kip1) is localized to the cytosol in Swiss/3T3 cells

Gang Wang, Robin Miskimins, W. Keith Miskimins

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

p27(Kip1) plays an important role in cell cycle progression by negatively regulating the activity of cyclin-Cdk complexes. To understand how p27(Kip1) functions, the level and subcellular location of p27(Kip1) in Swiss/3T3 cells following serum stimulation of quiescent cells was examined. Surprisingly, p27(Kip1) was observed exclusively in the cytosol throughout G1 and into early S phase. However, as expected, p27(Kip1) in the cytosolic fraction was greatly reduced following serum stimulation and reached very low levels by late G1. The decline in the level of p27(Kip1) corresponded in time to an increase in the nuclear level of both Cdk2 and cyclin E. In quiescent 3T3 cells Cdk2 was inactive and co-precipitated with p27(Kip1). After serum stimulation, both nuclear and cytosolic Cdk2 was activated and this corresponded to the decline in p27(Kip1). Overexpression of p27(Kip1) allowed accumulation of the inhibitor in the nucleus but inhibited entry of Cdk2 into the nucleus following serum stimulation. The subcellular localization of p27(Kip1) was also examined in a variety of other mammalian cells. In all the cell lines examined the preponderance of p27(Kip1) was found in the cytosolic fraction. However, a substantial level of nuclear p27(Kip1) was observed for several cell lines. In a primary mixed glial cell culture p27(Kip1) was localized to the nucleus. The results suggest that cytosolic p27(Kip1) has a functional role in regulating cell cycle progression, possibly through inhibiting transport of cyclin E-Cdk 2 complexes into the nucleus.

Original languageEnglish (US)
Pages (from-to)5204-5210
Number of pages7
JournalOncogene
Volume18
Issue number37
DOIs
StatePublished - Sep 16 1999

Keywords

  • Cdk2
  • Cell cycle
  • Cyclin E
  • p27(Kip1)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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