Fbxw7 in cell cycle exit and stem cell maintenance

Insight from gene-targeted mice

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3307-3313
Number of pages7
JournalCell Cycle
Volume7
Issue number21
DOIs
Publication statusPublished - Nov 1 2008

Fingerprint

Cell Cycle
Stem Cells
Maintenance
Genes
SKP Cullin F-Box Protein Ligases
F-Box Proteins
Phenotype
Cyclin E
Ubiquitination
Protein Subunits
Hematopoietic Stem Cells
Knockout Mice
Neoplasms
Fibroblasts
T-Lymphocytes
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Fbxw7 in cell cycle exit and stem cell maintenance : Insight from gene-targeted mice. / Onoyama, Ichiro; Nakayama, Keiichi.

In: Cell Cycle, Vol. 7, No. 21, 01.11.2008, p. 3307-3313.

Research output: Contribution to journalReview article

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