Document Detail


Fbxw7 in cell cycle exit and stem cell maintenance: insight from gene-targeted mice.
MedLine Citation:
PMID:  18948752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regulation of the exit of cells from the cell cycle is important in the development of multicellular organisms and is also implicated in the maintenance of stem cells. Furthermore, defects in cell cycle exit are thought to be a major cause of cancer. However, the mechanisms responsible for regulation of cell cycle exit have remained largely unknown. Fbxw7 is the F-box protein subunit of an SCF-type ubiquitin ligase complex that targets positive regulators of the cell cycle-including cyclin E, c-Myc, Notch and c-Jun-for ubiquitylation and subsequent degradation by the 26S proteasome in order to promote cell cycle exit. Consistent with such a function, mutations of the Fbxw7 gene have been detected in various human malignancies. We have recently generated conventional and conditional Fbxw7 knockout mice and examined stem cells, progenitor cells and differentiated cells in the mutant animals for cell cycle defects. Here we summarize the pleiotropic phenotypes of Fbxw7 deficiency in various cell types including T cells, hematopoietic stem cells and embryonic fibroblasts. Such phenotypes have provided insight into the biological roles of Fbxw7 in cell cycle exit, stem cell maintenance and oncosuppression.
Authors:
Ichiro Onoyama; Keiichi I Nakayama
Publication Detail:
Type:  Journal Article; Review     Date:  2008-11-05
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  7     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-12-23     Completed Date:  2009-02-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3307-13     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle*
F-Box Proteins / metabolism*
Gene Targeting*
Mice
Receptors, Notch / metabolism
Stem Cells / cytology*,  metabolism
T-Lymphocytes / cytology,  metabolism
Ubiquitin-Protein Ligases / deficiency,  metabolism*
Chemical
Reg. No./Substance:
0/F-Box Proteins; 0/Fbxw7 protein, mouse; 0/Receptors, Notch; EC 6.3.2.19/Ubiquitin-Protein Ligases

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