p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells

Nat Cell Biol. 1999 Aug;1(4):207-14. doi: 10.1038/12027.


The F-box protein p45SKP2 is the substrate-targeting subunit of the ubiquitin-protein ligase SCFSKP2 and is frequently overexpressed in transformed cells. Here we report that expression of p45SKP2 in untransformed fibroblasts activates DNA synthesis in cells that would otherwise growth-arrest. Expression of p45SKP2 in quiescent fibroblasts promotes p27Kip1 degradation, allows the generation of cyclin-A-dependent kinase activity and induces S phase. Coexpression of a degradation-resistant p27Kip1 mutant suppresses p45SKP2-induced cyclin-A-kinase activation and S-phase entry. We propose that p45SKP2 is important in the progression from quiescence to S phase and that the ability of p45SKP2 to promote p27Kip1 degradation is a key aspect of its S-phase-inducing function. In transformed cells, p45SKP2 may contribute to deregulated initiation of DNA replication by interfering with p27Kip1 function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Binding Sites
  • Cell Cycle / physiology
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Culture Media, Serum-Free
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / metabolism
  • DNA Replication
  • Gene Expression
  • Humans
  • Interphase / physiology
  • Microtubule-Associated Proteins / metabolism*
  • Mutation
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • S Phase / physiology*
  • S-Phase Kinase-Associated Proteins
  • Tumor Suppressor Proteins*


  • Cdkn1b protein, rat
  • Cell Cycle Proteins
  • Culture Media, Serum-Free
  • Microtubule-Associated Proteins
  • Recombinant Proteins
  • S-Phase Kinase-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases