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Efficient Internalization of the Polo-Box of Polo-like Kinase 1 Fused to an Antennapedia Peptide Results in Inhibition of Cancer Cell Proliferation¹

Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, 60590 Frankfurt, Germany

Polo-like kinases (Plk) regulate multiple stages in mitosis. Plk1 is overexpressed in tumors.The COOH-terminal regions of Plks contain a conserved domain, termed polo-box, which is required for subcellular localization and for physical interaction with substrates. We linked the polo-box (amino acids 410–429) of Plk1 to an Antennapedia peptide and studied its impact on tumor cells. Whereas the wild-type polo-box inhibited the proliferation of tumor cells associated with induction of apoptosis, a mutated derivative was much less effective. The treatment caused mitotic arrest, misaligned chromosomes, and multiple centrosomes. Taken together, membrane-permeable polo-box peptides inhibit cancer cell proliferation efficiently.

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