Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development.
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.
Mesh Terms:
Animals, Cell Cycle Proteins, Crosses, Genetic, Cullin Proteins, Embryo, Mammalian, Exons, F-Box Proteins, Female, Fetal Growth Retardation, Gene Targeting, Genotype, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Genetic, Phenotype, Placenta, Pregnancy, Protein Binding
Animals, Cell Cycle Proteins, Crosses, Genetic, Cullin Proteins, Embryo, Mammalian, Exons, F-Box Proteins, Female, Fetal Growth Retardation, Gene Targeting, Genotype, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Genetic, Phenotype, Placenta, Pregnancy, Protein Binding
Mol. Cell. Biol.
Date: Aug. 01, 2006
PubMed ID: 16880526
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