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Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter

Oncogene volume 21, pages 1563–1570 (2002)Cite this article

Abstract

E2F1 is a potent inducer of apoptosis whereas its relative, E2F4, generally does not promote cell death. Other work from our laboratory has demonstrated that E2F1 can directly bind and represss the Mcl-1 promoter – contributing to E2F1-mediated apoptosis. Here we show that while E2F1 can repress the Mcl-1 promoter, other members of the E2F family (such as E2F4) cannot. Characterization of the Mcl-1 promoter demonstrates that the −143/+10 region is critical for E2F1-mediated downregulation. We demonstrate that the ability of E2F1 to repress the Mcl-1 promoter correlates with its ability to bind within the required −143/+10 region of this promoter. In contrast, E2F4 is unable to bind to the −143/+10 region of the Mcl-1 promoter. We propose that E2F4 is unable to repress the Mcl-1 promoter primarily as a result of insufficient binding to the essential regulatory region. This is the first evidence of DNA binding specificity among E2F family members that results in differential regulation of a naturally occurring promoter.

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Acknowledgements

We thank Dr Eric Haura for helpful scientific discussion and comments on the manuscript. We also thank Drs Lanming Zhang and Marybeth Colter who performed DNA sequencing, and Mr Larry Kuba of the Molecular Imaging Core at H Lee Moffitt Cancer Center for assisting with the preparation of the manuscript. This work was supported by NCI Grant #CA78214 to WD Cress, by American Heart Association Southern Research Consortium Fellowship #9850018FRL to R Croxton, and by the H Lee Moffitt Comprehensive Cancer Center and Research Institute.

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Authors and Affiliations

  1. Program in Molecular Oncology, H Lee Moffitt Comprehensive Cancer Center and Research Institute, Tampa, 33612, Florida, FL, USA

    Rhonda Croxton, Yihong Ma & W Douglas Cress

  2. Department of Oncology, Tampa, 33612, Florida1, FL, USA

    Yihong Ma & W Douglas Cress

  3. Department of Biochemistry & Molecular Biology, Tampa, 33612, Florida, FL, USA

    Rhonda Croxton & W Douglas Cress

  4. Institute for Biomolecular Sciences, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Rhonda Croxton & W Douglas Cress

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  1. Rhonda Croxton
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Correspondence to W Douglas Cress.

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Croxton, R., Ma, Y. & Cress, W. Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter. Oncogene 21, 1563–1570 (2002). https://doi.org/10.1038/sj.onc.1205232

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