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

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.
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