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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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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DOI: https://doi.org/10.1038/sj.onc.1207649
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