Fbxw7 in cell cycle exit and stem cell maintenance: Insight from gene-targeted mice

研究成果: ジャーナルへの寄稿評論記事

29 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)3307-3313
ページ数7
ジャーナルCell Cycle
7
発行部数21
DOI
出版物ステータス出版済み - 11 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

これを引用

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

:: Cell Cycle, 巻 7, 番号 21, 01.11.2008, p. 3307-3313.

研究成果: ジャーナルへの寄稿評論記事

@article{d121464082e842cdb9b8951324c39394,
title = "Fbxw7 in cell cycle exit and stem cell maintenance: Insight from gene-targeted mice",
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.",
author = "Ichiro Onoyama and Nakayama, {Keiichi I.}",
year = "2008",
month = "11",
day = "1",
doi = "10.4161/cc.7.21.6931",
language = "English",
volume = "7",
pages = "3307--3313",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "21",

}

TY - JOUR

T1 - Fbxw7 in cell cycle exit and stem cell maintenance

T2 - Insight from gene-targeted mice

AU - Onoyama, Ichiro

AU - Nakayama, Keiichi I.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=55849100682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55849100682&partnerID=8YFLogxK

U2 - 10.4161/cc.7.21.6931

DO - 10.4161/cc.7.21.6931

M3 - Review article

C2 - 18948752

AN - SCOPUS:55849100682

VL - 7

SP - 3307

EP - 3313

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 21

ER -