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E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains

Oncogene volume 23, pages 5138–5150 (2004)Cite this article

Abstract

The E2F family of transcription factors play an important role in regulating cell cycle progression. We report here the characterization and functional properties of a new member of the human E2F family, referred to as E2F-7. E2F-7 has two separate DNA-binding domains, a feature that distinguishes E2F-7 from other mammalian E2F proteins, but resembling the organization of recently isolated E2F-like proteins from Arabidopsis. E2F-7 binds to DNA independently of a DP partner and delays cell cycle progression. Interestingly, E2F-7 modulates the transcription properties of other E2F proteins. A mutational analysis indicates that the integrity of both DNA-binding domains is required for cell cycle delay and transcriptional modulation. Biochemical results and protein modelling studies suggest that in binding to DNA interactions occur between the two DNA-binding domains, most probably as a homodimer, thereby mimicking the organization of an E2F/DP heterodimer. These structural and functional properties of E2F-7 imply a unique role in regulating cellular proliferation.

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Acknowledgements

We thank M Caldwell for help in preparing the paper, and Adam Inche for assistance with the figures. This work was supported by Cancer Research UK, the Medical Research Council and the EU.

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Author notes

  1. Nicola Logan and Laurent Delavaine: Both these authors contributed equally to this work

Authors and Affiliations

  1. Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK

    Nicola Logan, Laurent Delavaine, Anne Graham, Carmel Reilly & Nicholas B La Thangue

  2. Division of Protein Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Jon Wilson

  3. Division of Molecular Carcinogenesis, H-2, The Netherlands Cancer Institute, Plsemanlaan 121, Amsterdam, 1066 CX, The Netherlands

    Thijn R Brummelkamp, E Marielle Hijmans & René Bernards

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  1. Nicola Logan
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  2. Laurent Delavaine
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Correspondence to Nicholas B La Thangue.

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Logan, N., Delavaine, L., Graham, A. et al. E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains. Oncogene 23, 5138–5150 (2004). https://doi.org/10.1038/sj.onc.1207649

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