A reciprocal relationship between Rb and Skp2: implications for restriction point control, signal transduction to the cell cycle and cancer

Cell Cycle. 2008 Jan 1;7(1):24-7. doi: 10.4161/cc.7.1.5232. Epub 2007 Oct 30.


The identification of Skp2 as a direct E2F target has allowed us to document the existence of a positive feedback loop comprised of Rb-E2F, Skp2, p27 and cyclin E-cdk2. We have termed this set of regulatory molecules the Skp2 autoinduction loop. Interference with this loop selectively regulates cell cycle progression through the restriction point. We describe here how the Skp2 autoinduction loop may interact with other regulatory controls on the restriction point, and how the reciprocal relationship between Rb and Skp2 may affect signal transduction to the cell cycle and thinking about the role of Skp2 overexpression in cancers.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology
  • Feedback, Physiological / physiology*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Neoplasms / chemistry*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology*
  • S-Phase Kinase-Associated Proteins / genetics
  • S-Phase Kinase-Associated Proteins / physiology*
  • Signal Transduction / physiology*


  • Cell Cycle Proteins
  • Retinoblastoma Protein
  • S-Phase Kinase-Associated Proteins