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

Ryosuke Tsunematsu, Masaaki Nishiyama, Shuhei Kotoshiba, Toru Saiga, Takumi Kamura, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


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 FbxwS. 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.

Original languageEnglish
Pages (from-to)6157-6169
Number of pages13
JournalMolecular and cellular biology
Issue number16
Publication statusPublished - Aug 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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