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E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation

Oncogene volume 20, pages 910–920 (2001)Cite this article

Abstract

E2F-1 induces p53 accumulation and E2F-1 and p53 form a physical complex, which affects the ability of E2F-1 to activate transcription. We mapped the domains on E2F-1 that interact with p53 and found two p53-binding domains. To understand the functional consequences of the E2F-1/p53 association on p53 activities we identified the domains of E2F-1 that were responsible for the accumulation of p53. Unexpectedly, we found that the E2F-1 transactivation domain was dispensable for p53 induction. By contrast, further deletion of the DP-1 interaction/‘marked’ box domain eliminated p53 accumulation. Radiolabeling pulse/chase analysis demonstrated that E2F-1 caused post-translational stabilization of p53. Although E2F-1 caused the stabilization of p53, E2F-1 expression impaired p53-dependent transactivation. Thus, the E2F-1 : p53 interaction may provide a checkpoint function to inactivate overactive E2F-1, but the association may also inactivate p53 transactivation to allow cell cycle progression.

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Acknowledgements

We thank Yue Hou, Dana King, Hui Yang, Chunying Yang, and Elsie White for expert technical assistance. We also thank Dr Kristian Helin for the pCMV-E2F-1Δ374 plasmid and for the KH20 antibody, Dr William Kaelin for the pRC-CMV-E2F-1Δ24 plasmid (Krek et al., 1994, 1995), Drs Jiandong Chen and Tom Shenk for the GST-p53 vectors, Dr Jennifer Pietenpol for pBIG-p53, and Dr Peter Jones for the p14ARF reporter plasmid. We also thank the Vanderbilt-Ingram Cancer Center sequencing facility for support. This work was supported by National Institutes of Health (NIH) grants AG13726, CA64140 and CA77274, and American Cancer Society grant JFRA-591 (SW Hiebert), NIH grants DK44158 and CA76379 (JL Cleveland), CA63230 (G Zambetti), CA09346 (CM Eischen), NIH Core grant 5 P30 CA21765, by the American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital and by the Vanderbilt-Ingram Cancer Center. J Nip was a Leukemia and Lymphoma Society of America Special Fellow (Grant No. 3827-99).

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  1. John Nip

    Present address: Unilever Research US, 45 River Road, Edgewater, NJ 07020, USA

  2. David K Strom

    Present address: University of South Carolina, Aiken, SC 29803, USA

Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, Tennessee, USA

    John Nip, David K Strom & Scott W Hiebert

  2. Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, Tennessee, USA

    Christine M Eischen, John L Cleveland & Gerard P Zambetti

  3. Department of Biochemistry, University of Tennessee, Memphis, TN 38163, Tennessee, USA

    John L Cleveland & Gerard P Zambetti

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Nip, J., Strom, D., Eischen, C. et al. E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene 20, 910–920 (2001). https://doi.org/10.1038/sj.onc.1204171

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