Polo-like kinases and the orchestration of cell division

Barr, Francis A.; Silljé, Herman H W; Nigg, Erich A.

doi:10.1038/nrm1401

Cited by 995 publications

(1,070 citation statements)

References 118 publications

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“…In our study, AURKA, the main activator of PLK1 protein, was also down-regulated in the treated colon cancer cells in relation to their respective untreated controls, probably affecting centrosome maturation and microtubule dynamics during G2/M transition (Macürek et al 2008). In recent years, PLK1 has emerged as an important regulator in cell cycle progression (Barr et al 2004). PLK1 is known to play a pivotal role in the regulation of mitotic entry, chromosome segregation, and cytokinesis (Lowery et al 2005).…”

Section: Discussionsupporting

confidence: 48%

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

et al. 2012

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In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obtained from microarray analysis. Reverse transcription quantitative-PCR was used to confirm relative changes in mRNA levels of selected genes from microarrays. The selection of genes was based on their expression change, adjusted p value, and known biological function. According to genome-wide transcriptomics analysis, rosemary polyphenols altered the expression of *4 % of the genes covered by the Affymetrix Human Gene 1.0ST chip in both colon cancer cells. However, only *18 % of the differentially expressed genes were common to both cell lines, indicating markedly different expression profiles in response to the treatment. Differences in induction of G2/ M arrest observed by rosemary polyphenols in the two colon adenocarcinoma cell lines suggest that the extract may be differentially effective against tumors with specific mutational pattern. From our results, it is also concluded that rosemary polyphenols induced a low degree of apoptosis indicating that other multiple signaling pathways may contribute to colon cancer cell death.

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Section: Discussionsupporting

confidence: 48%

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

et al. 2012

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“…In this mechanism of Cdk1 activation, it is thought that both active Plk1 and Cdk1 prevent Wee1 and Myt1 inhibitory phosphorylations on Cdk1. Adapted from Barr et al, 2004and van Vugt and Medema, 2005(Barr et al, 2004van Vugt and Medema, 2005 Mitosis onset is signified by active Cdk1-Cyclin B translocation from the cytoplasm to the nucleus, which is regulated by a phosphorylation event on Cyclin B Hagting et al, 1999). It is postulated that nuclear translocation is mediated by Plk1 phosphorylation of Cyclin B (Toyoshima-Morimoto et al, 2001;Yuan et al, 2002).…”

Section: Figure 13 Cdk1 Activation Pathwaymentioning

confidence: 99%

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Smith¹,

Dejsuphong

Balestrini³

et al. 2009

Nat Cell Biol

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The effects of ATM and ATR signalling induced by chromosomal breakage have been described extensively in modulating cell cycle progression up to the onset of mitosis.However, DNA damage checkpoint responses in mitotic cells are not well understood.This thesis reports on the effects of double strand breaks on the progression of mitosis.We found ATM and ATR activation can occur in mitotic Xenopus laevis egg extract and the induction of ATM and ATR by chromosomal breakages inhibits spindle assembly in both Xenopus egg extract and somatic cells. The delay in mitotic progression induced by ATM and ATR was found not to involve major spindle assembly factors activities such as, Cdk1, Plx1 and RCC1/Ran-GTP. However, normal anastral spindles formation around linear DNA coated beads, which can activate ATM and ATR, linked centrosome-driven spindle assembly to ATM and ATR dependent spindle defects. cDNA expression library screening was undertaken to identify novel ATM and ATR targets in this mitotic checkpoint pathway, through which the novel centrosomal protein XCEP63 was identified as a likely candidate. Data obtained from depletion and reconstitution of XCEP63 in Xenopus egg extract established that normal centrosome-driven spindle assembly requires XCEP63. Moreover, ATM and ATR phosphorylates XCEP63 on serine 560 and promotes delocalisation from the centrosome. ATM and ATR inhibition or addition of non-phosphorylable XCEP63 recombinant protein mutated at serine 560 prevents spindle assembly abnormalities.These findings suggest that ATM and ATR regulate mitotic events by targeting XCEP63 and centrosome-dependent spindle assembly. This pathway may provide support for DNA repair processes or regulate cell survival in the presence of mitotic DNA damage. 3

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“…Among them, mammalian Plk1 and its M-phase homologs in other organisms are the most extensively studied. They are involved in many cellular events critical for cell division, including centrosome maturation and separation, mitotic entry, bipolar spindle formation, sister chromatid segregation and cytokinesis (Barr et al, 2004). Plk1 expression is closely linked to cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Plk1 depletion in nontransformed diploid cells activates the DNA-damage checkpoint

Lei

Erikson

2008

Oncogene

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We previously reported that polo-like kinase 1 (Plk1) depletion by lentivirus-based RNA interference led to mitotic arrest and apoptosis in cancer cells, whereas normal diploid cell lines, hTERT-RPE1 and MCF10A, survived a similar level of depletion. To study homogeneous cell lines, we generated several Plk1-depleted hTERT-RPE1 and MCF10A clones that were derived from single cells depleted of Plk1. We found that in the long term, Plk1 depletion slowed proliferation of hTERT-RPE1 cells, apparently due to attenuated progression through S phase. These cells had altered morphology and were elongated compared with control. In contrast, MCF10A clones with mild levels of depletion showed no obvious phenotype. They appeared to have normal proliferation rates with no cell-cycle arrest. However, one MCF10A clone, which was severely depleted of Plk1, although viable, showed sporadic G2/M arrest and apoptosis. This MCF10A clone and all the hTERT-RPE1 clones displayed evidence of DNA-damage checkpoint activation. These data further support the interpretation that cancer cell lines have a much greater requirement for Plk1 than normal nontransformed diploid cells.

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Polo-like kinases and the orchestration of cell division

Cited by 995 publications

References 118 publications

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Plk1 depletion in nontransformed diploid cells activates the DNA-damage checkpoint

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