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Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis

Santamaria, Anna and Neef, Rüdiger and Eberspächer, Uwe and Eis, Knut and Husemann, Manfred and Mumberg, Dominik and Prechtl, Stefan and Schulze, Volker and Siemeister, Gerhard and Wortmann, Lars and Barr, Francis A. and Nigg, Erich A.. (2007) Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis. Molecular Biology of the Cell, 18 (10). pp. 4024-4036.

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Abstract

Polo-like kinase 1 (Plk1) is a key regulator of mitotic progression and cell division in eukaryotes. It is highly expressed in tumor cells and considered a potential target for cancer therapy. Here, we report the discovery and application of a novel potent small-molecule inhibitor of mammalian Plk1, ZK-Thiazolidinone (TAL). We have extensively characterized TAL in vitro and addressed TAL specificity within cells by studying Plk1 functions in sister chromatid separation, centrosome maturation, and spindle assembly. Moreover, we have used TAL for a detailed analysis of Plk1 in relation to PICH and PRC1, two prominent interaction partners implicated in spindle assembly checkpoint function and cytokinesis, respectively. Specifically, we show that Plk1, when inactivated by TAL, spreads over the arms of chromosomes, resembling the localization of its binding partner PICH, and that both proteins are mutually dependent on each other for correct localization. Finally, we show that Plk1 activity is essential for cleavage furrow formation and ingression, leading to successful cytokinesis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Cell Biology
ISSN:1059-1524
e-ISSN:1939-4586
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:07 Nov 2017 07:12
Deposited On:22 Mar 2012 13:16

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