Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development

Mol Cell Biol. 2006 Aug;26(16):6157-69. doi: 10.1128/MCB.00595-06.


Cullin-based ubiquitin ligases (E3s) constitute one of the largest E3 families. Fbxw8 (also known as Fbw6 or Fbx29) is an F-box protein that is assembled with Cul7 in an SCF-like E3 complex. Here we show that Cul7 forms a heterodimeric complex with Cul1 in a manner dependent on Fbxw8. We generated mice deficient in Fbxw8 and found that Cul7 did not associate with Cul1 in cells of these mice. Two-thirds of Fbxw8-/- embryos die in utero, whereas the remaining one-third are born alive and grow to adulthood. Fbxw8-/- embryos show intrauterine growth retardation and abnormal development of the placenta, characterized by both a reduced thickness of the spongiotrophoblast layer and abnormal vessel structure in the labyrinth layer. Although the placental phenotype of Fbxw8-/- mice resembles that of Cul7-/- mice, other abnormalities of Cul7-/- mice are not apparent in Fbxw8-/- mice. These results suggest that the Cul7-based SCF-like E3 complex has both Fbxw8-dependent and Fbxw8-independent functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Crosses, Genetic
  • Cullin Proteins / metabolism*
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / pathology
  • Exons / genetics
  • F-Box Proteins / metabolism*
  • Female
  • Fetal Growth Retardation
  • Gene Targeting
  • Genotype
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Genetic
  • Phenotype
  • Placenta / abnormalities
  • Placenta / cytology
  • Placenta / embryology*
  • Placenta / pathology
  • Pregnancy
  • Protein Binding


  • Cell Cycle Proteins
  • Cul7 protein, mouse
  • Cullin 1
  • Cullin Proteins
  • F-Box Proteins
  • Fbxw8 protein, mouse