Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells

Schubert, Conrad von; Cubizolles, Fabien; Bracher, Jasmine M.; Sliedrecht, Tale; Kops, Geert J. P. L.; Nigg, Erich A.

doi:10.1016/j.celrep.2015.06.007

Cited by 113 publications

(131 citation statements)

References 56 publications

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“…For details, see Figs EV3, EV4 and EV5. Production of recombinant adenovirus‐associated virus (rAAV) particles and infection of cells were carried out as described previously (Berdougo et al , 2009; von Schubert et al , 2015). To establish the γ‐tubulin‐EGFP cell line, a FACSAria IIIu (BD Biosciences, San Jose, CA; USA) was used to isolate cells based on fluorescence.…”

Section: Methodsmentioning

confidence: 99%

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

et al. 2016

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Centrioles are essential for the formation of centrosomes and cilia. While numerical and/or structural centrosomes aberrations are implicated in cancer, mutations in centriolar and centrosomal proteins are genetically linked to ciliopathies, microcephaly, and dwarfism. The evolutionarily conserved mechanisms underlying centrosome biogenesis are centered on a set of key proteins, including Plk4, Sas‐6, and STIL, whose exact levels are critical to ensure accurate reproduction of centrioles during cell cycle progression. However, neither the intracellular levels of centrosomal proteins nor their stoichiometry within centrosomes is presently known. Here, we have used two complementary approaches, targeted proteomics and EGFP‐tagging of centrosomal proteins at endogenous loci, to measure protein abundance in cultured human cells and purified centrosomes. Our results provide a first assessment of the absolute and relative amounts of major components of the human centrosome. Specifically, they predict that human centriolar cartwheels comprise up to 16 stacked hubs and 1 molecule of STIL for every dimer of Sas‐6. This type of quantitative information will help guide future studies of the molecular basis of centrosome assembly and function.

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Section: Methodsmentioning

confidence: 99%

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

et al. 2016

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“…26 Concurrently, an independent study demonstrates that Plk1 phosphorylates MELT motifs in C. elegans that naturally lacks a recognizable gene for Mps1. This implies that functions commonly attributed to Mps1 in vertebrates are effectively substituted and executed by Plk1 in this nematode.…”

Section: The Ndc80 Complexmentioning

confidence: 99%

How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

Agarwal

Varma

2015

BioArchitecture

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ABSTRACT. Mitosis entails the bona fide segregation of duplicated chromosomes. This process is accomplished by the attachment of kinetochores on chromosomes to microtubules (MTs) of the mitotic spindle. Once the appropriate attachment is achieved, the spindle assembly checkpoint (SAC) that delays the premature onset of anaphase needs to be silenced for the cell to proceed to anaphase and cytokinesis. Therefore, while it is imperative to preserve the SAC when kinetochores are unattached, it is of paramount importance that SAC components are removed post kinetochore microtubule (kMT) attachment. Precise knowledge of how kMT attachments trigger the removal of SAC components from kinetochores or how the checkpoint proteins feedback in to the attachment machinery remains elusive. This review aims to describe the recent advances that provide an insight into the interplay of molecular events that coordinate and regulate the SAC activity in response to kMT attachment during cell division.

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“…It is mainly located in different subcellular structures based on the PBD and phosphorylation of Thr 210 [1,5]. It is involved in the regulation of Mps1, Bub3, Mad1, and other proteins [9]. In human somatic cells, inhibited Plk1 leads to multiple mitotic defects, including the formation of abnormal spindles, misaligned chromosomes and i mproper chromosom e condensation [10].…”

Section: Introductionmentioning

confidence: 99%

Plk1 inhibition leads to a failure of mitotic division during the first mitotic division in pig embryos

Zhang

Chen

Cui

et al. 2017

J Assist Reprod Genet

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Purpose This study was conducted to examine the dynamic distribution of polo-like 1 kinase (Plk1) and the possible role it plays in first mitotic division during early porcine embryo development. Methods Indirect immunofluorescence and confocal microscopy imaging techniques combined with western blot analyses were used to study the dynamic expression and subcellular localization of Plk1 protein in pig parthenogenetic embryos. Finally, a selective Plk1 inhibitor, GSK461364, was used to evaluate the potential role of Plk1 during this special stage.Results The results showed that Plk1 upon expression exhibited specific dynamic intracellular localization, which closely correlated with the α-tubulin distribution during the first mitotic division. GSK461364 treatment resulted in cleavage failure, with majority of the GSK461364-treated embryos being arrested in prometaphase. Further results of the subcellular structure examination showed that GSK461364 treatment led to a significantly higher proportion of the treated embryos having abnormal spindles and misarranged chromosomes at the prometaphase stage. Conclusions Thus, these results indicated that Plk1 is essential for porcine embryos to complete the first mitotic division. Furthermore, Plk1 regulation was associated with effects on spindle assembly and chromosome arrangement.

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Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells

Cited by 113 publications

References 56 publications

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

Plk1 inhibition leads to a failure of mitotic division during the first mitotic division in pig embryos

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