Efficient internalization of the polo-box of polo-like kinase 1 fused to an Antennapedia peptide results in inhibition of cancer cell proliferation.
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.
Yuan
Juping
J
Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, 60590 Frankfurt, Germany.
Krämer
Andrea
A
Eckerdt
Frank
F
Kaufmann
Manfred
M
Strebhardt
Klaus
K
D000595:Amino Acid Sequence; D051943:Antennapedia Homeodomain Protein; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D002877:Chromosomes, Human / Q000187:drug effects; D017124:Conserved Sequence; D016195:G2 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008941:Spindle Apparatus / Q000187:drug effects; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000097869:Polo-Like Kinase 1
D051943:Antennapedia Homeodomain Protein; D018797:Cell Cycle Proteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000097869:Polo-Like Kinase 1