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Polo-like kinases and oncogenesis

Oncogene volume 24, pages 267–276 (2005)Cite this article

Abstract

Polo-like kinases (Plks) play pivotal roles in the regulation of cell cycle progression. Plk1, the best characterized family member among mammalian Plks, strongly promotes the progression of cells through mitosis. Furthermore, Plk1 is found to be overexpressed in a variety of human tumors and its expression correlates with cellular proliferation and prognosis of tumor patients. Although all Plks share two conserved elements, the N-terminal Ser/Thr kinase domain and a highly homologues C-terminal region termed the polo-box motif, their functions diverge considerably. While Plk1 is inhibited by different checkpoint pathways, Plk2 and Plk3 are activated by the spindle checkpoint or the DNA damage checkpoint. Thus, Plk2 and Plk3 seem to inhibit oncogenic transformation. Deregulation of Plk1 activity contributes to genetic instability, which in turn leads to oncogenic transformation. In contrast, Plk2 and Plk3 are involved in checkpoint-mediated cell cycle arrest to ensure genetic stability, thereby inhibiting the accumulation of genetic defects. In this review, we shall discuss the roles of Plks in oncogenesis and Plk1 as a target for therapeutic intervention against cancer.

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Abbreviations

Plk1:

Polo-like kinase 1

PB:

polo box

PBD:

polo-box domain

APC:

anaphase-promoting complex

dnPlk1:

dominant-negative Plk1

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Acknowledgements

We would like to thank Dr Ferris for providing unpublished data. The work in our laboratory is supported in part by the Nationales Genomforschungsnetz (Grant KR-S07T01 to KS), the Deutsche Krebshilfe (Grant 10-1212-St 1 to KS), from the Deutsche Forschungsgemeinschaft (Grant STR/8-1 to KS), the Messer Stiftung and the Sander Stiftung.

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  1. Frank Eckerdt

    Present address: Department of Pharamacology, University of Colorado, School of Medicine, Denver, 80262, USA

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  1. Department of Gynecology and Obstetrics, Medical School, JW Goethe-University, Theodor-Stern-Kai 7, Frankfurt, D-60590, Germany

    Frank Eckerdt, Juping Yuan & Klaus Strebhardt

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Eckerdt, F., Yuan, J. & Strebhardt, K. Polo-like kinases and oncogenesis. Oncogene 24, 267–276 (2005). https://doi.org/10.1038/sj.onc.1208273

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