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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7018
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pubmed:dateCreated |
2004-12-16
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pubmed:abstractText |
The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability. 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/F-Box Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBXW7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fbxw7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1476-4687
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
432
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
775-9
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pubmed:dateRevised |
2011-5-23
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pubmed:meshHeading |
pubmed-meshheading:15592418-Animals,
pubmed-meshheading:15592418-Base Sequence,
pubmed-meshheading:15592418-Cell Cycle Proteins,
pubmed-meshheading:15592418-Cell Transformation, Neoplastic,
pubmed-meshheading:15592418-F-Box Proteins,
pubmed-meshheading:15592418-Female,
pubmed-meshheading:15592418-Fibroblasts,
pubmed-meshheading:15592418-Gene Deletion,
pubmed-meshheading:15592418-Genes, Tumor Suppressor,
pubmed-meshheading:15592418-Loss of Heterozygosity,
pubmed-meshheading:15592418-Male,
pubmed-meshheading:15592418-Mice,
pubmed-meshheading:15592418-Mice, Knockout,
pubmed-meshheading:15592418-Mutation,
pubmed-meshheading:15592418-Neoplasms,
pubmed-meshheading:15592418-RNA, Messenger,
pubmed-meshheading:15592418-RNA, Small Interfering,
pubmed-meshheading:15592418-Survival Rate,
pubmed-meshheading:15592418-Tumor Suppressor Protein p53,
pubmed-meshheading:15592418-Ubiquitin-Protein Ligases
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pubmed:year |
2004
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pubmed:articleTitle |
Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene.
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pubmed:affiliation |
Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, California 94143, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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