Inactivation of E2F3 results in centrosome amplification. Cancer Cell 2003 Apr;3(4):333-46
Date
05/03/2003Pubmed ID
12726860Pubmed Central ID
PMC3033013DOI
10.1016/s1535-6108(03)00083-7Scopus ID
2-s2.0-0042510099 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
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.
Author List
Saavedra HI, Maiti B, Timmers C, Altura R, Tokuyama Y, Fukasawa K, Leone GAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AneuploidyAnimals
Blotting, Western
Cell Cycle
Cells, Cultured
Centrosome
Cyclin E
Cyclin-Dependent Kinases
DNA Replication
E2F3 Transcription Factor
Embryo, Mammalian
Fibroblasts
Flow Cytometry
Immunohistochemistry
Mice
Mice, Knockout
Nuclear Proteins
Transcription Factors
