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 Celljournal_title
Molecular biology of the cellauthors
Santamaria A,Neef R,Eberspächer U,Eis K,Husemann M,Mumberg D,Prechtl S,Schulze V,Siemeister G,Wortmann L,Barr FA,Nigg EAdoi
10.1091/mbc.e07-05-0517subject
Has Abstractpub_date
2007-10-01 00:00:00pages
4024-36issue
10eissn
1059-1524issn
1939-4586pii
E07-05-0517journal_volume
18pub_type
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