Roles of Polo-like Kinase 1 in the Assembly of Functional Mitotic Spindles

Sumara, Izabela; Giménez-Abián, Juan F.; Gerlich, Daniel W.; Hirota, Toru; Kraft, Claudine; Torre, Consuelo de la; Ellenberg, Jan; Peters, Jan‐Michael

doi:10.1016/j.cub.2004.09.049

Cited by 316 publications

(356 citation statements)

References 52 publications

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“…Treatment of the human osteosarcoma cell line U20S with 25 M DAP-81 for 4 h was found to suppress the recruitment of ␥-tubulin to the centrosomes and induce monopolar spindles in a high percentage of treated cells, a phenotype often observed after Plk1 depletion by RNAi (Figure 2). Centrosomes were also often found outside of the microtubule arrays, as previously observed in siRNAtreated cells (13). Moreover, in quantitative immunofluorescence assays, a dosedependent reduction of phospho-Cdc25C with saturating concentrations at 6 M was observed.…”

supporting

confidence: 80%

Small Molecules Keep Mitotic Kinases in Check

Strebhardt

2006

ACS Chem. Biol.

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The remarkable progress in the discovery of small molecules that target protein kinases continues, and two recent reports have described alternative approaches to this task: homology modeling and phenotype-based screening. Compounds targeting the nucleotide binding pockets of polo-like kinases in particular provide significant new insights into the molecular mechanisms controlling cell-division phenotypes.

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supporting

confidence: 80%

Small Molecules Keep Mitotic Kinases in Check

Strebhardt

2006

ACS Chem. Biol.

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“…We speculate that this is mediated through Plk1-dependent regulation of Centrobin because of the overlap in phenotypes of Centrobin-and Plk1-depleted cells. The similarities include unfocused spindle poles, activation of the spindle checkpoint and a lack of stable microtubule-kinetochore attachments (Sumara et al, 2004). This would most likely occur directly through the phosphorylation of Centrobin, which contains a number of putative Plk1 phosphorylation sites.…”

Section: Discussionmentioning

confidence: 99%

Centrobin regulates the assembly of functional mitotic spindles

et al. 2010

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The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubulekinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle.

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“…After 4 h, nocodazole was added to the cells. Time points were taken at 0, 3,6,8,10, and 12 h. This particular experiment was repeated three times with varying time points to gauge the time windows for appropriate measurements. Phosphorylation sites on CDC27 were used to check the reproducibility of the kinetics between experiments.…”

Section: Methodsmentioning

confidence: 99%

Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: A quantitative proteomic analysis

Steen¹,

Steen

Georgi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The anaphase promoting complex (APC) controls the degradation of proteins during exit from mitosis and entry into S-phase. The activity of the APC is regulated by phosphorylation during mitosis. Because the phosphorylation pattern provides insights into the complexity of regulation of the APC, we studied in detail the phosphorylation patterns at a single mitotic state of arrest generated by various antimitotic drugs. We examined the phosphorylation patterns of the APC in HeLa S3 cells after they were arrested in prometaphase with taxol, nocodazole, vincristine, or monastrol. There were 71 phosphorylation sites on nine of the APC subunits. Despite the common state of arrest, the various antimitotic drug treatments resulted in differences in the phosphorylation patterns and phosphorylation stoichiometries. The relative phosphorylation stoichiometries were determined by using a method adapted from the isotope-free quantitation of the extent of modification (iQEM). We could show that during drug arrest the phosphorylation state of the APC changes, indicating that the mitotic arrest is not a static condition. We discuss these findings in terms of the variable efficacy of antimitotic drugs in cancer chemotherapy. mass spectrometry ͉ stable isotope free quantitation ͉ prometaphase ͉ cell cycle arrest

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Roles of Polo-like Kinase 1 in the Assembly of Functional Mitotic Spindles

Cited by 316 publications

References 52 publications

Small Molecules Keep Mitotic Kinases in Check

Small Molecules Keep Mitotic Kinases in Check

Centrobin regulates the assembly of functional mitotic spindles

Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: A quantitative proteomic analysis

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