RSK2 is a kinetochore-associated protein that participates in the spindle assembly checkpoint

Vigneron, Suzanne; Brioudes, Estelle; Burgess, Andrew; Labbé, Jean‐Claude; Lorca, Thierry

doi:10.1038/onc.2010.105

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…The NTD of RSK2 transduces its substrates to accept the RSK2 activation signal [29]. Mad1 is a member of the Myc/Max/Mad family and a substrate of p90 ribosomal kinase and p70S6 kinase [30][31][32]. We showed that myricetin inhibits HGC-27 and SGC7901 cell proliferation through Mad1 and RSK2.…”

Section: Discussionmentioning

confidence: 94%

Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells

et al. 2015

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Myricetin is a flavonoid that is abundant in fruits and vegetables and has protective effects against cancer and diabetes. However, the mechanism of action of myricetin against gastric cancer (GC) is not fully understood. We researched myricetin on the proliferation, apoptosis, and cell cycle in GC HGC-27 and SGC7901 cells, to explore the underlying mechanism of action. Cell Counting Kit (CCK)-8 assay, Western blotting, cell cycle analysis, and apoptosis assay were used to evaluate the effects of myricetin on cell proliferation, apoptosis, and the cell cycle. To analyze the binding properties of ribosomal S6 kinase 2 (RSK2) with myricetin, surface plasmon resonance (SPR) analysis was performed. CCK8 assay showed that myricetin inhibited GC cell proliferation. Flow cytometry analysis showed that myricetin induces apoptosis and cell cycle arrest in GC cells. Western blotting indicated that myricetin influenced apoptosis and cell cycle arrest of GC cells by regulating related proteins. SPR analysis showed strong binding affinity of RSK2 and myricetin. Myricetin bound to RSK2, leading to increased expression of Mad1, and contributed to inhibition of HGC-27 and SGC7901 cell proliferation. Our results suggest the therapeutic potential of myricetin in GC.

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Section: Discussionmentioning

confidence: 94%

Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells

et al. 2015

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“…Finally, as RSK2 phosphorylated TIN2, and inhibiting this kinase in mitotic cells reduced TIN2 phosphorylation, TIN2 phosphorylation may be linked with functions of RSK2. In this regard, RSK2 promotes G2/M transition [35] and maintains spindle assembly checkpoint [36]. In summary, we demonstrate that first, only the two sites S295 and S330 in TIN2 are found to be phosphorylated, second, these two sites are preferentially phosphorylated at mitosis and third, RSK2 can phosphorylate TIN2 on these two residues.…”

Section: Discussionmentioning

confidence: 57%

Cell Cycle Regulated Phosphorylation of the Telomere-Associated Protein TIN2

Yang

Counter

2013

PLoS ONE

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The protein TIN2 is a member of telomere-binding protein complex that serves to cap and protect mammalian chromosome ends. As a number of proteins in this complex are phosphorylated in a cell cycle-dependent manner, we investigated whether TIN2 is modified by phosphorylation as well. We performed phospho-proteomic analysis of human TIN2, and identified two phosphorylated residues, serines 295 and 330. We demonstrated that both these sites were phosphorylated during mitosis in human cells, as detected by Phos-tag reagent and phosphorylation-specific antibodies. Phosphorylation of serines 295 and 330 appeared to be mediated, at least in part, by the mitotic kinase RSK2. Specifically, phosphorylation of TIN2 at both these residues was increased upon expression of RSK2 and reduced by an inhibitor of the RSK family of kinases. Moreover, RSK2 phosphorylated TIN2 in vitro. The identification of these specifically timed post-translational events during the cell cycle suggests a potential mitotic regulation of TIN2 by phosphorylation.

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“…7), the latter of which has similar indications in lower organisms (72). Whether low MSK2 expression is a cause or consequence of aneuploidy is unknown, but based on previous findings of a prolonged G1 phase in MSK2-deficient cells (44) and that a closely related family member is a kinetochore-associated protein that participates in the spindle assembly checkpoint (73), it is likely that reduced MSK2 expression prevents the localization and function of several proteins involved in cell cycle progression. Thus, further investigation is required to determine whether MSK2 prevents aneuploidy generation directly or indirectly via DNMT1 , AURKA / AURKB and/or other cell cycle associated genes and the exact mechanism by which MSK2 mediates its function.…”

Section: Discussionmentioning

confidence: 99%

Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres

Chavez

McElroy

Bossert

et al. 2014

Human Molecular Genetics

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A map of human embryo development that combines imaging, molecular, genetic and epigenetic data for comparisons to other species and across pathologies would be greatly beneficial for basic science and clinical applications. Here, we compared mRNA and protein expression of key mediators of DNA methylation and histone modifications between mouse and human embryos, embryos from fertile/infertile couples, and following growth factor supplementation. We observed that individual mouse and human embryos are characterized by similarities and distinct differences in DNA methylation and histone modification patterns especially at the single-cell level. In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage. Likewise, differences in epigenetic mediator expression were also observed between embryos from fertile and infertile couples, which were largely equalized in response to growth factor supplementation, suggesting that select growth factors might prevent alterations in epigenetic profiles during prolonged embryo culture. Finally, we determined that reduced expression via morpholino technologies of a single histone-modifying enzyme, Rps6ka4/Msk2, resulted in cleavage-stage arrest as assessed by time-lapse imaging and was associated with aneuploidy generation. Taken together, data document differences in epigenetic patterns between species with implications for fertility and suggest functional roles for individual epigenetic factors during pre-implantation development.

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RSK2 is a kinetochore-associated protein that participates in the spindle assembly checkpoint

Cited by 11 publications

References 24 publications

Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells

Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells

Cell Cycle Regulated Phosphorylation of the Telomere-Associated Protein TIN2

Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres

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