Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery

Macůrek, Libor; Lindqvist, Arne; Lim, Desmond R.; Lampson, Michael A.; Klompmaker, Rob; Freire, Raimundo; Clouin, Christophe; Taylor, Stephen S.; Yaffe, Michael B.; Medema, René H.

doi:10.1038/nature07185

Cited by 609 publications

(804 citation statements)

References 31 publications

Supporting

Mentioning

751

Contrasting

Unclassified

Order By: Relevance

“…A significant number of moderately down-regulated genes related with M phase, chromosome segregation and cytokinesis, enriched data sets obtained in gene expression microarray analysis. 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).…”

Section: Discussionsupporting

confidence: 50%

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 50%

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Under these conditions treatment with MLN8054 also prevented phosphorylation on a wellcharacterized Aurora A site on Polo-like kinase (T210). 31,32 Genetic inhibition of Aurora A activity using siRNAs also resulted in elevated levels of BimEL in mitosis ( Figure 6c). As phosphorylation of the bTrCP1 degron is required for interaction with BimEL, we determined if MLN8054 affects this interaction.…”

Section: Resultsmentioning

confidence: 94%

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

et al. 2013

View full text Add to dashboard Cite

“…Interestingly, there is some overlap in the mechanisms of action of these two classes of drugs as aurora kinases are also involved in cell division and Plk1 is activated by aurora A [24]. However, both kinases have different effects on the mitotic process [18].…”

Section: Discussionmentioning

confidence: 99%

The polo-like kinase inhibitor BI 2536 exhibits potent activity against malignant plasma cells and represents a novel therapy in multiple myeloma

Stewart

Kishikova

Powell

et al. 2011

Experimental Hematology

View full text Add to dashboard Cite

Objective. Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536. Materials and Methods. We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis. We have also examined the effect of the microenvironment on these parameters and the effects of BI 2536 in combination with other antimyeloma agents. Results. We show that MM cell lines and patient samples express PLK1 and that cell death by apoptosis occurs when Plk1 is inhibited. Cells treated with BI 2536 accumulate in the G 2 /M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells. Conclusions. Plk1 inhibition leads to cell death in MM cell lines and patient myeloma samples. Our data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma. Ó

show abstract

Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery

Cited by 609 publications

References 31 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

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

The polo-like kinase inhibitor BI 2536 exhibits potent activity against malignant plasma cells and represents a novel therapy in multiple myeloma

Contact Info

Product

Resources

About