Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene

Jian-Hua Mao, Jesus Perez-losada, Di Wu, Reyno DelRosario, Ryosuke Tsunematsu, Keiichi I. Nakayama, Ken Brown, Sheila Bryson and Allan Balmain ()
Additional contact information
Jian-Hua Mao: University of California at San Francisco
Jesus Perez-losada: University of California at San Francisco
Di Wu: University of California at San Francisco
Reyno DelRosario: University of California at San Francisco
Ryosuke Tsunematsu: Kyushu University
Keiichi I. Nakayama: Kyushu University
Ken Brown: University of Glasgow
Sheila Bryson: University of Glasgow
Allan Balmain: University of California at San Francisco

Nature, 2004, vol. 432, issue 7018, 775-779

Abstract: Abstract The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability1. Here we identify the mouse Fbxw7 gene as a p53-dependent tumour suppressor gene by using a mammalian genetic screen for p53-dependent genes involved in tumorigenesis. Radiation-induced lymphomas from p53+/- mice, but not those from p53-/- mice, show frequent loss of heterozygosity and a 10% mutation rate of the Fbxw7 gene. Fbxw7+/- mice have greater susceptibility to radiation-induced tumorigenesis, but most tumours retain and express the wild-type allele, indicating that Fbxw7 is a haploinsufficient tumour suppressor gene. Loss of Fbxw7 alters the spectrum of tumours that develop in p53 deficient mice to include a range of tumours in epithelial tissues such as the lung, liver and ovary. Mouse embryo fibroblasts from Fbxw7-deficient mice, or wild-type mouse cells expressing Fbxw7 small interfering RNA, have higher levels of Aurora-A kinase, c-Jun and Notch4, but not of cyclin E. We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers.

Date: 2004
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature03155 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:432:y:2004:i:7018:d:10.1038_nature03155

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature03155

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().