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Molecular and Cellular Biology, July 2004, p. 6467-6475, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6467-6475.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The E4F Protein Is Required for Mitotic Progression during Embryonic Cell Cycles

Laurent Le Cam,1,{dagger} Matthieu Lacroix,2 Maria A. Ciemerych,1,{ddagger} Claude Sardet,2 and Piotr Sicinski1*

Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115,1 Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, IFR122, 34293 Montpellier, France2

Received 15 January 2004/ Returned for modification 29 February 2004/ Accepted 9 April 2004

The ubiquitously expressed E4F protein was originally identified as an E1A-regulated cellular transcription factor required for adenovirus replication. The function of this protein in normal cell physiology remains largely unknown. To address this issue, we generated E4F knockout mice by gene targeting. Embryos lacking E4F die at the peri-implantation stage, while in vitro-cultured E4F–/– blastocysts exhibit defects in mitotic progression, chromosomal missegregation, and increased apoptosis. Consistent with these observations, we found that E4F localizes to the mitotic spindle during the M phase of early embryos. Our results establish a crucial role for E4F during early embryonic cell cycles and reveal an unexpected function for E4F in mitosis.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617) 632-5005. Fax: (617) 632-5006. E-mail: peter_sicinski{at}dfci.harvard.edu.

{dagger} Present address: Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, IFR122, Montpellier, France.

{ddagger} Present address: Department of Embryology, Institute of Zoology, Warsaw University, 02-096 Warsaw, Poland.

Molecular and Cellular Biology, July 2004, p. 6467-6475, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6467-6475.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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