This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsunematsu, R. Articles by Nakayama, K. I. Search for Related Content PubMed PubMed Citation Articles by Tsunematsu, R. Articles by Nakayama, K. I.

 Previous Article  |  Next Article 

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.

Fbxw8 Is Essential for Cul1-Cul7 Complex Formation and for Placental Development

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.

This article has been cited by other articles:

• Tsutsumi, T., Kuwabara, H., Arai, T., Xiao, Y., DeCaprio, J. A. (2008). Disruption of the Fbxw8 Gene Results in Pre- and Postnatal Growth Retardation in Mice. Mol. Cell. Biol. 28: 743-751 [Abstract] [Full Text]  
• Jung, P., Verdoodt, B., Bailey, A., Yates, J. R. III, Menssen, A., Hermeking, H. (2007). Induction of Cullin 7 by DNA damage attenuates p53 function. Proc. Natl. Acad. Sci. USA 104: 11388-11393 [Abstract] [Full Text]  
• Kaustov, L., Lukin, J., Lemak, A., Duan, S., Ho, M., Doherty, R., Penn, L. Z., Arrowsmith, C. H. (2007). The Conserved CPH Domains of Cul7 and PARC Are Protein-Protein Interaction Modules That Bind the Tetramerization Domain of p53. J. Biol. Chem. 282: 11300-11307 [Abstract] [Full Text]  
• Skaar, J. R., Florens, L., Tsutsumi, T., Arai, T., Tron, A., Swanson, S. K., Washburn, M. P., DeCaprio, J. A. (2007). PARC and CUL7 Form Atypical Cullin RING Ligase Complexes. Cancer Res. 67: 2006-2014 [Abstract] [Full Text]