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

Oncogene

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

Published: August 2003

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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http://dx.doi.org/10.1038/sj.onc.1206495DOI Listing

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