An integrated view of cyclin E function and regulation

Cell Cycle. 2012 Jan 1;11(1):57-64. doi: 10.4161/cc.11.1.18775. Epub 2012 Jan 1.


Cancers of diverse cell lineages express high levels of cyclin E, and in various studies, cyclin E overexpression correlates with increased tumor aggression. One way that normal control of cyclin E expression is disabled in cancer cells is via loss-of-function mutations sustained by FBXW7. This gene encodes the Fbw7 tumor suppressor protein that provides substrate specificity for a ubiquitin ligase complex that targets multiple oncoproteins for degradation. Numerous other mechanisms besides Fbw7 mutations can deregulate cyclin E expression and activity in cancer cells. Recent reports demonstrate that inappropriate cyclin E expression may have far-reaching biological consequences for cell physiology, including altering gene expression programs governing proliferation, differentiation, survival and senescence. In this review, we discuss the function of mammalian cyclin E in the context of these new data as well as the complex network that connects cyclin E functions to the cellular controls regulating its expression and activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • E2F Transcription Factors / metabolism
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • F-Box-WD Repeat-Containing Protein 7
  • Gene Knock-In Techniques
  • Humans
  • Interphase
  • Mice
  • Phosphorylation
  • Substrate Specificity
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism


  • Cell Cycle Proteins
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • E2F Transcription Factors
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • Ubiquitin-Protein Ligases
  • Cyclin-Dependent Kinase 2