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

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.

journal_name

Mol Biol Cell

authors

Santamaria A,Neef R,Eberspächer U,Eis K,Husemann M,Mumberg D,Prechtl S,Schulze V,Siemeister G,Wortmann L,Barr FA,Nigg EA

doi

10.1091/mbc.e07-05-0517

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

4024-36

issue

10

eissn

1059-1524

issn

1939-4586

pii

E07-05-0517

journal_volume

18

pub_type

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