Regulation of the cell cycle at the G1-S transition by proteolysis of cyclin E and p27Kip1

Biochem Biophys Res Commun. 2001 Apr 13;282(4):853-60. doi: 10.1006/bbrc.2001.4627.


The transition from G1 phase to S phase of the mammalian cell cycle is controlled by many positive and negative regulators, among which cyclin E and p27Kip1, respectively, undergo the most marked changes in concentration at this transition. The abundance of both cyclin E and p27Kip1 is regulated predominantly by posttranslational mechanisms, in particular by proteolysis mediated by the ubiquitin-proteasome pathway. Cyclin E and p27Kip1 each bind to and undergo polyubiquitination by the same ubiquitin ligase, known as SCF(Skp2). The degradation of cyclin E and p27Kip1 is greatly impaired in Skp2-deficient mice, resulting in intracellular accumulation of these proteins. In this article, recent progress in characterization of the molecular mechanisms that control the proteolysis of cyclin E and p27Kip1 is reviewed.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins*
  • Cell Cycle*
  • Cyclin E / metabolism*
  • Cyclin E / physiology
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cysteine Endopeptidases / metabolism
  • G1 Phase
  • Ligases / genetics
  • Ligases / metabolism
  • Ligases / physiology
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / metabolism*
  • Microtubule-Associated Proteins / physiology
  • Models, Biological
  • Multienzyme Complexes / metabolism
  • Neoplasms / metabolism
  • Peptide Synthases / metabolism
  • Polyploidy
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational
  • S Phase
  • SKP Cullin F-Box Protein Ligases
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism


  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Cyclin E
  • Microtubule-Associated Proteins
  • Multienzyme Complexes
  • Tumor Suppressor Proteins
  • Ubiquitins
  • Cyclin-Dependent Kinase Inhibitor p27
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Ligases
  • Peptide Synthases