Cdc20 control of cell fate during prolonged mitotic arrest

Nilsson, Jakob

doi:10.1002/bies.201100094

Cited by 15 publications

(7 citation statements)

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“…FACS analysis of the tagged SUMO2 cell line revealed that this synchronization protocol resulted in a G2/M arrest (Figure S1A and Materials and Methods S1) and visual inspection of cells by microscopy revealed that they were arrested in prometaphase. The addition of taxol to the medium arrests cells in prometaphase by activating the spindle assembly checkpoint [26]. A very efficient and synchronous mitotic exit was achieved from taxol-arrested cells by inhibition of Aurora B with ZM447439 [27], as revealed by the rapid disappearance of Cyclin B1 and Aurora A already one hour after inhibitor addition (Figure 2B).…”

Section: Resultsmentioning

confidence: 96%

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

et al. 2014

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During mitosis large alterations in cellular structures occur rapidly, which to a large extent is regulated by post-translational modification of proteins. Modification of proteins with the small ubiquitin-related protein SUMO2/3 regulates mitotic progression, but few mitotic targets have been identified so far. To deepen our understanding of SUMO2/3 during this window of the cell cycle, we undertook a comprehensive proteomic characterization of SUMO2/3 modified proteins in mitosis and upon mitotic exit. We developed an efficient tandem affinity purification strategy of SUMO2/3 modified proteins from mitotic cells. Combining this purification strategy with cell synchronization procedures and quantitative mass spectrometry allowed for the mapping of numerous novel targets and their dynamics as cells progressed out of mitosis. This identified RhoGDIα as a major SUMO2/3 modified protein, specifically during mitosis, mediated by the SUMO ligases PIAS2 and PIAS3. Our data provide a rich resource for further exploring the role of SUMO2/3 modifications in mitosis and cell cycle regulation.

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Section: Resultsmentioning

confidence: 96%

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

et al. 2014

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“…APC/C forms a protein complex with its mitotic coactivator, CDC20, which controls mitotic progression [59]. CDC20 protein level may directly affect cell fate during prolonged mitotic arrest [60] and its turnover rate may be a key factor in cancer patient response to antimitotic therapies [61]. …”

Section: Resultsmentioning

confidence: 99%

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Huang

Chang

Lin

et al. 2014

BioMed Research International

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Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

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“…Previously, Nilsson (2011) has suggested that the level of Cdc20 might be one of the key features determining response to anti-mitotic cancer therapeutics. Downregulation of Cdc20 in breast cancer cells has been associated with inhibition of cell proliferation in vitro (Jiang et al , 2011, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cdc20 and securin overexpression predict short-term breast cancer survival

et al. 2014

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Background:Cdc20 is an essential component of cell division and responsible for anaphase initiation regulated by securin degradation. Cdc20 function is strongly regulated by the spindle assembly checkpoint to ensure the timely separation of sister chromatids and integrity of the genome. We present the first results on Cdc20 in a large clinical breast cancer material.Methods:The study was based on 445 breast cancer patients with up to 20 years of follow-up (mean 10.0 years). DNA content was determined by image cytometry on cell imprints, and Cdc20 and securin immunohistochemistry on tissue microarrays of breast cancer tissue.Results:In our results, high Cdc20 and securin expression was associated with aneuploid DNA content. In prognostic analyses, high Cdc20 immunoexpression alone and in combination with high securin immunoexpression indicated aggressive course of disease and up to 6.8-fold (P<0.001) risk of breast cancer death. Particularly, high Cdc20 and securin immunoexpression identified a patient subgroup with extremely short, on average 2.4 years, breast cancer survival and triple-negative breast cancer (TNBC) subtype.Conclusions:We report for the first time the association of high Cdc20 and securin immunoexpression with extremely poor outcome of breast cancer patients. Our experience indicates that Cdc20 and securin are promising candidates for clinical applications in breast cancer prognostication, especially in the challenging prognostic decisions of TNBC.

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Cdc20 control of cell fate during prolonged mitotic arrest

Cited by 15 publications

References 73 publications

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Cdc20 and securin overexpression predict short-term breast cancer survival

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