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Inhibition of cell proliferation and induction of apoptosis by novel tetravalent peptides inhibiting DNA binding of E2F

Oncogene volume 22, pages 4943–4952 (2003)Cite this article

Abstract

We have isolated several peptides from random peptide phage display libraries that specifically recognize the cell cycle regulatory transcription factor E2F and inhibit DNA binding of E2F/DP heterodimers (E2F-1, E2F-2, E2F-3, E2F-4 or E2F–5, and DP-1). The inhibitory efficiency could be strongly enhanced by generating branched tetravalent molecules. To analyse the biological consequences of peptide-mediated E2F inhibition, we fused two of these branched molecules to a cell-penetrating peptide derived from the HTV-Tat protein. Incubation of human tumor cells with these branched Tat-containing peptides led to an inhibition of cell proliferation and induction of apoptosis. These results provide new insights into the function of E2F and further validate E2F as a potential therapeutic target in proliferative diseases.

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Acknowledgements

We thank Marylou Zuzarte for FACS analyses and Dr M Krause (IMT) for oligonucleotide and peptide synthesis. This work was supported by a grant from the Deutsche Forschungsgemeinschaft to REK (SFB 397) and the Dr Mildred Scheel Stiftung für Krebsforschung to RM.

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Author notes

  1. Silvia Montigiani

    Present address: Chiron S.p.A., Via Fiorentina 1, 53100, Siena, Italy

  2. Roland E Kontermann

    Present address: Vectron Therapeutics AG, Rudolf-Breitscheid-Str. 24, 35037, Marburg, Germany

Authors and Affiliations

  1. Institute of Molecular Biology and Tumor Research (IMT), Philipps-University, Emil-Mannkopff-Strasse 2, Marburg, D-35033, Germany

    Silvia Montigiani, Rolf Müller & Roland E Kontermann

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  1. Silvia Montigiani
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  2. Rolf Müller
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Correspondence to Rolf Müller.

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Montigiani, S., Müller, R. & Kontermann, R. Inhibition of cell proliferation and induction of apoptosis by novel tetravalent peptides inhibiting DNA binding of E2F. Oncogene 22, 4943–4952 (2003). https://doi.org/10.1038/sj.onc.1206495

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