Yuan Juping, Krämer Andrea, Eckerdt Frank, Kaufmann Manfred, Strebhardt Klaus
Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, 60590 Frankfurt, Germany.
Cancer Res. 2002 Aug 1;62(15):4186-90.
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.
Polo样激酶（Plk）调节有丝分裂的多个阶段。Plk1在肿瘤中过表达。Plk的COOH末端区域包含一个保守结构域，称为polo框，它是亚细胞定位和与底物物理相互作用所必需的。我们将Plk1的polo框（氨基酸410 - 429）与触角足肽连接，并研究了其对肿瘤细胞的影响。野生型polo框抑制与凋亡诱导相关的肿瘤细胞增殖，而突变衍生物的效果则要差得多。该处理导致有丝分裂停滞、染色体排列不齐和多个中心体。综上所述，可透过细胞膜的polo框肽能有效抑制癌细胞增殖。
