ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores

Isokane, Mayumi; Walter, Thomas; Mahen, Robert; Nijmeijer, Bianca; Hériché, Jean‐Karim; Miura, Kota; Maffini, Stefano; Ivanov, Miroslav P; Kitajima, Tomoya S.; Peters, Jan‐Michael; Ellenberg, Jan

doi:10.1083/jcb.201408089

Cited by 21 publications

(33 citation statements)

References 54 publications

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“…This novel localization of the mitotic kinase AURKB suggests that it is an integral part of the contractile cytokinetic ring. While unexpected, this observation is consistent with AURKB's function in cytokinesis [20][21][22] . This raises the very interesting possibility that the midplane and cytokinetic ring pools of AURKB have different functions for central spindle architecture and cytokinesis respectively during mitotic exit.…”

Section: Methods; Supplemental Datasupporting

confidence: 76%

Experimental and computational framework for a dynamic protein atlas of human cell division

Yin

Hossain

Hèriché

et al. 2017

Preprint

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SUMMARYEssential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, timing of interactions and changes in cellular structure are all crucial to ensure correct assembly, function and regulation of protein complexes1-4. Live cell imaging can reveal protein distributions and dynamics but experimental and theoretical challenges prevented its use to produce quantitative data and a model of mitosis that comprehensively integrates information and enables analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries.To address this, we generated a 4D image data-driven, canonical model of the morphological changes during mitotic progression of human cells. We used this model to integrate dynamic 3D concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy5. The approach taken here in the context of the MitoSys consortium to generate a dynamic protein atlas of human cell division is generic. It can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types and can be conceptually transferred to other cellular functions.

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Section: Methods; Supplemental Datasupporting

confidence: 76%

Experimental and computational framework for a dynamic protein atlas of human cell division

Yin

Hossain

Hèriché

et al. 2017

Preprint

Self Cite

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“…TTK is overexpressed in various cancers and has previously been studied as a target for the treatment of BC, glioblastoma, ovarian cancer, colon cancer, and others (18,19,(32)(33)(34)(35). TTK has been well characterized for its role in the spindle assembly checkpoint (SAC) complex, which prevents progression from metaphase to anaphase in mitosis when problems occur in metaphase (36)(37)(38)(39)(40). Previously, TTK inhibition has been shown to cause irregular mitosis as well as increased aneuploidy, lagging chromosomes, and mitotic catastrophe (41,42).…”

Section: Resultsmentioning

confidence: 99%

TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination

Chandler¹,

Moubadder²,

Ritter³

et al. 2020

Journal of Clinical Investigation

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tumor volume was calculated using the equation: volume = (length × width 2) × π/6. Additive and synergistic effects were calculated using the FTV method as previously described (59, 60). Study approval. The protocols used in this study were approved by the IACUC of the University of Michigan. Statistics. Statistical analyses were performed using GraphPad Prism 7.0 (GraphPad Software). A log-rank (Mantel-Cox) test was used for survival curve analyses. One-way ANOVA was performed for BC subtype analysis. A 2-sided Student's t test and 1-way ANOVA with Dunnett's multiple comparisons test were used for in vitro statistical analyses. A 1-way ANOVA with Dunnett's multiple comparisons test and a log-rank (Mantel-Cox) test were used for in vivo analyses. A P value of 0.05 or less was considered statistically significant.

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“…S1E ). It was recently suggested that ARHGEF17 bound to Mps1 is involved in the rapid turnover of Mps1 on kinetochores 46 ; it would be interesting to see how ARFGEF17 is related to the regulation of Mps1 localization by microtubules.…”

Section: Discussionmentioning

confidence: 99%

Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis

Ikeda

Tanaka

2017

Sci Rep

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For faithful chromosome segregation, the formation of stable kinetochore–microtubule attachment and its monitoring by the spindle assembly checkpoint (SAC) are coordinately regulated by mechanisms that are currently ill-defined. Here, we show that polo-like kinase 1 (Plk1), which is instrumental in forming stable kinetochore–microtubule attachments, is also involved in the maintenance of SAC activity by binding to Bub1, but not by binding to CLASP2 or CLIP-170. The effect of Plk1 on the SAC was found to be mediated through phosphorylation of Mps1, an essential kinase for the SAC, as well as through phosphorylation of the MELT repeats in Knl1. Bub1 acts as a platform for assembling other SAC components on the phosphorylated MELT repeats. We propose that Bub1-bound Plk1 is important for the maintenance of SAC activity by supporting Bub1 localization to kinetochores in prometaphase, a time when the kinetochore Mps1 level is reduced, until the formation of stable kinetochore-microtubule attachment is completed. Our study reveals an intricate mechanism for coordinating the formation of stable kinetochore–microtubule attachment and SAC activity.

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ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores

Abstract: The spindle assembly checkpoint (SAC) ensures genome stability during cell division. Here, a new essential SAC factor, ARHGEF17, is characterized by quantitative imaging, biochemical, and biophysical experiments, which show that it targets the checkpoint kinase Mps1 to kinetochores.

Cited by 21 publications

References 54 publications

Experimental and computational framework for a dynamic protein atlas of human cell division

Experimental and computational framework for a dynamic protein atlas of human cell division

TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination

Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis

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