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Molecular and Cellular Biology, August 2006, p. 6157-6169, Vol. 26, No. 16
0270-7306/06/$08.00+0 doi:10.1128/MCB.00595-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582,1 CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012,Japan2
Received 6 April 2006/ Returned for modification 22 May 2006/ Accepted 6 June 2006
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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