Inactivation of E2F3 results in centrosome amplification.
The E2F family of transcription factors is critical for the control of cell cycle progression. We now show that the specific inactivation of E2F3 in mouse embryo fibroblasts (MEFs) results in a disruption of the centrosome duplication cycle. Loss of E2F3, but not E2F1, E2F2, E2F4, or E2F5 results in unregulated cyclin E-dependent kinase activity, defects in nucleophosmin B association with centrosomes, and premature centriole separation and duplication. Consequently, this defect leads to centrosome amplification, mitotic spindle defects, and aneuploidy. Our findings implicate the E2F3 transcription factor as an important link that orchestrates DNA and centrosome duplication cycles, ensuring the faithful transmission of genetic material to daughter cells.
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Children's Research Institute, The Ohio State University, Columbus, OH 43210, USA.
Harold I
HI
Saavedra
Baidehi
B
Maiti
Cynthia
C
Timmers
Rachel
R
Altura
Yukari
Y
Tokuyama
Kenji
K
Fukasawa
Gustavo
G
Leone
D000782:Aneuploidy; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology*; D019927:Cyclin E; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D050699:E2F3 Transcription Factor; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000502:physiology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D014157:Transcription Factors / Q000235:genetics*
D019927:Cyclin E; D050699:E2F3 Transcription Factor; C490840:E2f3 protein, mouse; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D000090243:Nucleophosmin; D018844:Cyclin-Dependent Kinases