First Author | Tsunematsu R | Year | 2006 |
Journal | Mol Cell Biol | Volume | 26 |
Issue | 16 | Pages | 6157-69 |
PubMed ID | 16880526 | Mgi Jnum | J:111403 |
Mgi Id | MGI:3653956 | Doi | 10.1128/MCB.00595-06 |
Citation | Tsunematsu R, et al. (2006) Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development. Mol Cell Biol 26(16):6157-69 |
abstractText | 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. |