期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 26, 期 16, 页码 6157-6169出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00595-06
关键词
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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 Cu17 forms a heterodimeric complex with Cull in a manner dependent on Fbxw8. We generated mice deficient in Fbxw8 and found that Cu17 did not associate with Cull 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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