Regulation of the Cell Cycle by SCF-type Ubiquitin Ligases

Semin Cell Dev Biol. 2005 Jun;16(3):323-33. doi: 10.1016/j.semcdb.2005.02.010.

Abstract

Regulation of the cell cycle is dependent on protein degradation by the ubiquitin-proteasome system. Two major ubiquitin ligases, the anaphase-promoting complex or cyclosome (APC/C) and SCF complex, are responsible for the periodic proteolysis of many regulators of the cell cycle. The receptor component of the SCF complex is one of many F-box proteins, three of which--Skp2, Fbw7, and beta-TrCP--are well characterized and implicated in cell cycle regulation. We have generated mice deficient in Skp2, Fbw7, or beta-TrCP1 and have identified the roles of these proteins in both cell cycle regulation and mouse development. Clinical evidence also suggests that dysregulation of these F-box proteins contributes to human cancers.

Publication types

  • Review

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / physiology
  • F-Box Proteins / physiology
  • F-Box-WD Repeat-Containing Protein 7
  • Humans
  • Mice
  • Mice, Knockout
  • Oncogene Proteins / metabolism
  • S-Phase Kinase-Associated Proteins / physiology
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / physiology*
  • Signal Transduction
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / physiology
  • Ubiquitin-Protein Ligases / physiology
  • beta-Transducin Repeat-Containing Proteins / physiology

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Fbxw7 protein, mouse
  • Oncogene Proteins
  • S-Phase Kinase-Associated Proteins
  • beta-Transducin Repeat-Containing Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases