Back to Search
Start Over
Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis
- Publication Year :
- 2007
- Publisher :
- American Society for Cell Biology, 2007.
-
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.
- Subjects :
- Cell division
Cleavage furrow formation
Mitosis
Cell Cycle Proteins
Spindle Apparatus
Biology
Chromatids
Protein Serine-Threonine Kinases
PLK1
Mice
Cell Line, Tumor
Proto-Oncogene Proteins
Mitotic Index
Animals
Humans
Molecular Biology
Protein Kinase Inhibitors
Cytokinesis
Centrosome
Aniline Compounds
urogenital system
DNA Helicases
Cell Biology
Articles
Cell biology
Enzyme Activation
Spindle checkpoint
Thiazolidines
PRC1
Anaphase
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9883ac2191d68738d0d6ed1fcb551b13
- Full Text :
- https://doi.org/10.5451/unibas-ep1733