Efficient internalization of the polo-box of polo-like kinase 1 fused to an Antennapedia peptide results in inhibition of cancer cell proliferation

Juping Yuan; Andrea Krämer; Frank Eckerdt; Manfred Kaufmann; Klaus Strebhardt

Efficient internalization of the polo-box of polo-like kinase 1 fused to an Antennapedia peptide results in inhibition of cancer cell proliferation

Cancer Res. 2002 Aug 1;62(15):4186-90.

Authors

Juping Yuan¹, Andrea Krämer, Frank Eckerdt, Manfred Kaufmann, Klaus Strebhardt

Affiliation

¹ Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, 60590 Frankfurt, Germany.

PMID: 12154015

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antennapedia Homeodomain Protein
Apoptosis / drug effects
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Cycle Proteins
Chromosomes, Human / drug effects
Conserved Sequence
G2 Phase / drug effects
Growth Inhibitors / genetics
Growth Inhibitors / metabolism*
Growth Inhibitors / pharmacology*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Homeodomain Proteins / pharmacology*
Humans
Mitosis / drug effects
Molecular Sequence Data
Nuclear Proteins*
Polo-Like Kinase 1
Protein Kinases / genetics
Protein Kinases / metabolism*
Protein Kinases / pharmacology*
Protein Serine-Threonine Kinases
Protein Structure, Tertiary
Proto-Oncogene Proteins
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Recombinant Fusion Proteins / pharmacology
Spindle Apparatus / drug effects
Transcription Factors*
Tumor Cells, Cultured

Substances

Antennapedia Homeodomain Protein
Cell Cycle Proteins
Growth Inhibitors
Homeodomain Proteins
Nuclear Proteins
Proto-Oncogene Proteins
Recombinant Fusion Proteins
Transcription Factors
Protein Kinases
Protein Serine-Threonine Kinases