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Takeo Kishimoto - One of the best experts on this subject based on the ideXlab platform.
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sgk phosphorylates cdc25 and myt1 to trigger <B>CyclinB> B cdk1 activation at the meiotic g2 m transition
Journal of Cell Biology, 2019Co-Authors: Daisaku Hiraoka, Kazuyoshi Chiba, Enako Hosoda, Takeo KishimotoAbstract:The kinase <B>CyclinB> B-Cdk1 complex is a master regulator of M-phase in Both mitosis and meiosis. At the G2/M transition, <B>CyclinB> B-Cdk1 activation is initiated By a trigger that reverses the Balance of activities Between Cdc25 and Wee1/Myt1 and is further accelerated By autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to Be the <B>CyclinB> A-Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce <B>CyclinB> B-Cdk1 activation, <B>CyclinB> A-Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation in starfish oocytes. Upon hormonal stimulation of the meiotic G2/M transition, SGK is activated By cooperation Between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.
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SGK phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation at the meiotic G2/M transition.
Journal of Cell Biology, 2019Co-Authors: Daisaku Hiraoka, Kazuyoshi Chiba, Enako Hosoda, Takeo KishimotoAbstract:The kinase <B>CyclinB> B-Cdk1 complex is a master regulator of M-phase in Both mitosis and meiosis. At the G2/M transition, <B>CyclinB> B-Cdk1 activation is initiated By a trigger that reverses the Balance of activities Between Cdc25 and Wee1/Myt1 and is further accelerated By autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to Be the <B>CyclinB> A-Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce <B>CyclinB> B-Cdk1 activation, <B>CyclinB> A-Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation in starfish oocytes. Upon hormonal stimulation of the meiotic G2/M transition, SGK is activated By cooperation Between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.
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SGK phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation at the meiotic G2/M transition
2018Co-Authors: Daisaku Hiraoka, Kazuyoshi Chiba, Enako Hosoda, Takeo KishimotoAbstract:The kinase <B>CyclinB> B-Cdk1 complex is a master regulator of M-phase in Both mitosis and meiosis. At the G2/M transition, <B>CyclinB> B-Cdk1 activation is initiated By a trigger that reverses the Balance of activities Between Cdc25 and Wee1/Myt1, and is further accelerated By autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to Be the <B>CyclinB> A-Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce <B>CyclinB> B-Cdk1 activation, <B>CyclinB> A-Cdk1 is non-essential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation in starfish oocytes. After hormonal stimulation of the meiotic G2/M transition, SGK is activated By cooperation Between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.
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sgk phosphorylates cdc25 and myt1 to trigger <B>CyclinB> B cdk1 activation at the meiotic g2 m transition
bioRxiv, 2018Co-Authors: Daisaku Hiraoka, Kazuyoshi Chiba, Enako Hosoda, Takeo KishimotoAbstract:The kinase <B>CyclinB> B-Cdk1 complex is a master regulator of M-phase in Both mitosis and meiosis. At the G2/M transition, <B>CyclinB> B-Cdk1 activation is initiated By a trigger that reverses the Balance of activities Between Cdc25 and Wee1/Myt1, and is further accelerated By autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to Be the <B>CyclinB> A-Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce <B>CyclinB> B-Cdk1 activation, <B>CyclinB> A-Cdk1 is non-essential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger <B>CyclinB> B-Cdk1 activation in starfish oocytes. After hormonal stimulation of the meiotic G2/M transition, SGK is activated By cooperation Between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.
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<B>CyclinB> B cdk1 inhiBits protein phosphatase pp2a B55 via a greatwall kinase independent mechanism
Journal of Cell Biology, 2014Co-Authors: Eiichi Okumura, Takeo Kishimoto, Atsushi Morita, Mizuho Wakai, Satoru Mochida, Masatoshi HaraAbstract:Entry into M phase is governed By <B>CyclinB> B–Cdk1, which undergoes Both an initial activation and suBsequent autoregulatory activation. A key part of the autoregulatory activation is the <B>CyclinB> B–Cdk1–dependent inhiBition of the protein phosphatase 2A (PP2A)–B55, which antagonizes <B>CyclinB> B–Cdk1. Greatwall kinase (Gwl) is Believed to Be essential for the autoregulatory activation Because Gwl is activated downstream of <B>CyclinB> B–Cdk1 to phosphorylate and activate α-endosulfine (Ensa)/Arpp19, an inhiBitor of PP2A-B55. However, <B>CyclinB> B–Cdk1 Becomes fully activated in some conditions lacking Gwl, yet how this is accomplished remains unclear. We show here that <B>CyclinB> B–Cdk1 can directly phosphorylate Arpp19 on a different conserved site, resulting in inhiBition of PP2A-B55. Importantly, this novel Bypass is sufficient for <B>CyclinB> B–Cdk1 autoregulatory activation. Gwl-dependent phosphorylation of Arpp19 is nonetheless necessary for downstream mitotic progression Because chromosomes fail to segregate properly in the aBsence of Gwl. Such a Biphasic regulation of Arpp19 results in different levels of PP2A-B55 inhiBition and hence might govern its different cellular roles.
Robert Bellé - One of the best experts on this subject based on the ideXlab platform.
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Model of the delayed translation of <B>CyclinB> B maternal mRNA after sea urchin fertilization.
Molecular reproduction and development, 2016Co-Authors: Vincent Picard, Odile Mulner-lorillon, Julia Morales, Patrick Cormier, Jérémie Bourdon, Anne Siegel, Robert BelléAbstract:Sea urchin eggs exhiBit a cap-dependent increase in protein synthesis within minutes after fertilization. This rise in protein synthesis occurs at a constant rate for a great numBer of proteins translated from the different availaBle mRNAs. Surprisingly, we found that <B>CyclinB> B, a major cell-cycle regulator, follows a synthesis pattern that is distinct from the gloBal protein population, so we developed a mathematical model to analyze this dissimilarity in Biosynthesis kinetic patterns. The model includes two pathways for <B>CyclinB> B mRNA entry into the translational machinery: one from immediately availaBle mRNA (mRNA<B>CyclinB>B) and one from mRNA activated solely after fertilization (XXmRNA<B>CyclinB>B). Two coefficients, α and β, were added to fit the measured scales of gloBal protein and <B>CyclinB> B synthesis, respectively. The model was simplified to identify the synthesis parameters and to allow its simulation. The calculated parameters for activation of the specific <B>CyclinB> B synthesis pathway after fertilization included a kinetic constant (ka ) of 0.024 sec-1 , for the activation of XXmRNA<B>CyclinB>B, and a critical time interval (t2 ) of 42 min. The proportion of XXmRNA<B>CyclinB>B form was also calculated to Be largely dominant over the mRNA<B>CyclinB>B form. Regulation of <B>CyclinB> B Biosynthesis is an example of a select protein whose translation is controlled By pathways that are distinct from housekeeping proteins, even though Both involve the same cap-dependent initiation pathway. Therefore, this model should help provide insight to the signaling utilized for the Biosynthesis of <B>CyclinB> B and other select proteins. Mol. Reprod. Dev. 83: 1070-1082, 2016. © 2016 Wiley Periodicals, Inc.
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pesticide roundup provokes cell division dysfunction at the level of cdk1 <B>CyclinB> B activation
Chemical Research in Toxicology, 2002Co-Authors: Julie Marc, Sandrine Boulben, Dorothee Hureau, Gaël Durand, Odile Mulnerlorillon, Robert BelléAbstract:To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin emBryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin emBryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could Be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a suBthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy Between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/<B>CyclinB> B regulates universally the M-phase of the cell cycle, we analyzed CDK1/<B>CyclinB> B activation during the first division of early development. Roundup delayed the activation of CDK1/<B>CyclinB> B in vivo. Roundup inhiBited also the gloBal protein synthetic rate without preventing the accumulation of <B>CyclinB> B. In summary, Roundup affects cell cycle regulation By delaying activation of the CDK1/<B>CyclinB> B complex, By synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/<B>CyclinB> B regulator, our results question the safety of glyphosate and Roundup on human health.
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Pesticide Roundup provokes cell division dysfunction at the level of CDK1/<B>CyclinB> B activation.
Chemical research in toxicology, 2002Co-Authors: Julie Marc, Odile Mulner-lorillon, Sandrine Boulben, Dorothee Hureau, Gaël Durand, Robert BelléAbstract:To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin emBryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin emBryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could Be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a suBthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy Between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/<B>CyclinB> B regulates universally the M-phase of the cell cycle, we analyzed CDK1/<B>CyclinB> B activation during the first division of early development. Roundup delayed the activation of CDK1/<B>CyclinB> B in vivo. Roundup inhiBited also the gloBal protein synthetic rate without preventing the accumulation of <B>CyclinB> B. In summary, Roundup affects cell cycle regulation By delaying activation of the CDK1/<B>CyclinB> B complex, By synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/<B>CyclinB> B regulator, our results question the safety of glyphosate and Roundup on human health.
Jordan W. Raff - One of the best experts on this subject based on the ideXlab platform.
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Hsp90 is required to localise <B>CyclinB> B and Msps/ch-TOG to the mitotic spindle in Drosophila and humans.
Journal of cell science, 2007Co-Authors: Renata Basto, Fanni Gergely, Viji M Draviam, Hiroyuki Ohkura, Kathryn Liley, Jordan W. RaffAbstract:During mitosis, <B>CyclinB> B is extremely dynamic and although it is concentrated at the centrosomes and spindle microtuBules (MTs) in organisms ranging from yeast to humans, the mechanisms that determine its localisation are poorly understood. To understand how <B>CyclinB> B is targeted to different locations in the cell we have isolated proteins that interact with <B>CyclinB> B in Drosophila emBryo extracts. Here we show that <B>CyclinB> B interacts with the molecular chaperone Hsp90 and with the MT-associated protein (MAP) Mini spindles (Msps; the Drosophila orthologue of XMAP215/ch-TOG). Both Hsp90 and Msps are concentrated at centrosomes and spindles, and we show that Hsp90, But not Msps, is required for the efficient localisation of <B>CyclinB> B to these structures. We find that, unlike what happens with other cell cycle proteins, Hsp90 is not required to staBilise <B>CyclinB> B or Msps during mitosis. Thus, we propose that Hsp90 plays a novel role in regulating the localisation of <B>CyclinB> B and Msps during mitosis.
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The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of <B>CyclinB> B in space and time
The Journal of cell biology, 2002Co-Authors: Jordan W. Raff, Kim Jeffers, Jun-yong HuangAbstract:In Drosophila cells <B>CyclinB> B is normally degraded in two phases: (a) destruction of the spindle-associated <B>CyclinB> B initiates at centrosomes and spreads to the spindle equator; and (B) any remaining cytoplasmic <B>CyclinB> B is degraded slightly later in mitosis. We show that the APC/C regulators Fizzy (Fzy)/Cdc20 and Fzy-related (Fzr)/Cdh1 Bind to microtuBules in vitro and associate with spindles in vivo. Fzy/Cdc20 is concentrated at kinetochores and centrosomes early in mitosis, whereas Fzr/Cdh1 is concentrated at centrosomes throughout the cell cycle. In syncytial emBryos, only Fzy/Cdc20 is present, and only the spindle-associated <B>CyclinB> B is degraded at the end of mitosis. A destruction Box-mutated form of <B>CyclinB> B (<B>CyclinB> B triple-point mutant [CBTPM]-GFP) that cannot Be targeted for destruction By Fzy/Cdc20, is no longer degraded on spindles in syncytial emBryos. However, CBTPM-GFP can Be targeted for destruction By Fzr/Cdh1. In cellularized emBryos, which normally express Fzr/Cdh1, CBTPM-GFP is degraded throughout the cell But with slowed kinetics. These findings suggest that Fzy/Cdc20 is responsiBle for catalyzing the first phase of <B>CyclinB> B destruction that occurs on the mitotic spindle, whereas Fzr/Cdh1 is responsiBle for catalyzing the second phase of <B>CyclinB> B destruction that occurs throughout the cell. These oBservations have important implications for the mechanisms of the spindle checkpoint.
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the roles of fzy cdc20 and fzr cdh1 in regulating the destruction of <B>CyclinB> B in space and time
Journal of Cell Biology, 2002Co-Authors: Jordan W. Raff, Kim Jeffers, Jun-yong HuangAbstract:In Drosophila cells <B>CyclinB> B is normally degraded in two phases: (a) destruction of the spindle-associated <B>CyclinB> B initiates at centrosomes and spreads to the spindle equator; and (B) any remaining cytoplasmic <B>CyclinB> B is degraded slightly later in mitosis. We show that the APC/C regulators Fizzy (Fzy)/Cdc20 and Fzy-related (Fzr)/Cdh1 Bind to microtuBules in vitro and associate with spindles in vivo. Fzy/Cdc20 is concentrated at kinetochores and centrosomes early in mitosis, whereas Fzr/Cdh1 is concentrated at centrosomes throughout the cell cycle. In syncytial emBryos, only Fzy/Cdc20 is present, and only the spindle-associated <B>CyclinB> B is degraded at the end of mitosis. A destruction Box-mutated form of <B>CyclinB> B (<B>CyclinB> B triple-point mutant [CBTPM]-GFP) that cannot Be targeted for destruction By Fzy/Cdc20, is no longer degraded on spindles in syncytial emBryos. However, CBTPM-GFP can Be targeted for destruction By Fzr/Cdh1. In cellularized emBryos, which normally express Fzr/Cdh1, CBTPM-GFP is degraded throughout the cell But with slowed kinetics. These findings suggest that Fzy/Cdc20 is responsiBle for catalyzing the first phase of <B>CyclinB> B destruction that occurs on the mitotic spindle, whereas Fzr/Cdh1 is responsiBle for catalyzing the second phase of <B>CyclinB> B destruction that occurs throughout the cell. These oBservations have important implications for the mechanisms of the spindle checkpoint.
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Centrosomes have a role in regulating the destruction of <B>CyclinB> B in early Drosophila emBryos.
Current biology : CB, 2000Co-Authors: James G. Wakefield, Jun-yong Huang, Jordan W. RaffAbstract:We reported previously that the disappearance of <B>CyclinB> B at the end of mitosis in early Drosophila emBryos starts at centrosomes and spreads into the spindle [1]. Here, we used a novel mutation, centrosome fall off (cfo), to investigate whether centrosomes are required to initiate the disappearance of <B>CyclinB> B from the spindle. In emBryos laid By homozygous cfo mutant mothers, the centrosomes co-ordinately detached from the mitotic spindle during mitosis, and the centrosomeless spindles arrested at anaphase. <B>CyclinB> B levels decreased on the detached centrosomes, But not on the arrested centrosomeless spindles, presumaBly explaining why the spindles arrest in anaphase in these emBryos. We found that the expression of a non-degradaBle <B>CyclinB> B in emBryos also caused an anaphase arrest, But most centrosomes remained attached to the arrested spindles, and non-degradaBle <B>CyclinB> B levels remained high on Both the centrosomes and spindles. These findings suggest that the disappearance of <B>CyclinB> B from centrosomes and spindles is closely linked to its destruction, and that a connection Between centrosomes and spindles is required for the proper destruction of the spindle-associated <B>CyclinB> B in early Drosophila emBryos. These results may have important implications for the mechanism of the spindle-assemBly checkpoint, as they suggest that unattached kinetochores may arrest cells in mitosis, at least in part, By signalling to centrosomes to Block the initiation of <B>CyclinB> B destruction.
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The disappearance of <B>CyclinB> B at the end of mitosis is regulated spatially in Drosophila cells.
The EMBO journal, 1999Co-Authors: Jun-yong Huang, Jordan W. RaffAbstract:We have followed the Behaviour of a <B>CyclinB> B–green fluorescent protein (GFP) fusion protein in living Drosophila emBryos in order to study how the localization and destruction of <B>CyclinB> B is regulated in space and time. We show that the fusion protein accumulates at centrosomes in interphase, in the nucleus in prophase, on the mitotic spindle in prometaphase and on the microtuBules that overlap in the middle of the spindle in metaphase. In cellularized emBryos, toward the end of metaphase, the spindle‐associated <B>CyclinB> B–GFP disappears from the spindle in a wave that starts at the spindle poles and spreads to the spindle equator; when the <B>CyclinB> B–GFP on the spindle is almost undetectaBle, the chromosomes enter anaphase, and any remaining cytoplasmic <B>CyclinB> B–GFP then disappears over the next few minutes. The endogenous <B>CyclinB> B protein appears to Behave in a similar manner. These findings suggest that the inactivation of <B>CyclinB> B is regulated spatially in Drosophila cells. We show that the anaphase‐promoting complex/cyclosome (APC/C) specifically interacts with microtuBules in emBryo extracts, But it is not confined to the spindle in mitosis, suggesting that the spatially regulated disappearance of <B>CyclinB> B may reflect the spatially regulated activation of the APC/C.
E Karsenti - One of the best experts on this subject based on the ideXlab platform.
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Regulation of Cdc2 <B>CyclinB>-B Activation By Ran, a Ras-Related Gtpase
Journal of Cell Science, 1995Co-Authors: P R Clarke, C Klebe, A Wittinghofer, E KarsentiAbstract:During the cell cycle, a checkpoint prevents the initiation of mitosis until S-phase is completed. The molecular mechanism may involve the RCC1 protein, which catalyses guanine nucleotide exchange on the Ras-related nuclear protein, Ran (or TC4). Genetic studies have suggested that RCC1 may Be involved in sensing the replication state of DNA and controlling the activation of Cdc2/<B>CyclinB> B protein kinase through Ran. In this report, we present direct Biochemical evidence for the post-translational control of Cdc2/<B>CyclinB> B activation By Ran. In a cell-free system of concentrated Xenopus egg extracts supplemented with nuclei, a mutant form of Ran (T24N) analogous to dominant inactive mutants of other Ras-related GTPases inhiBits Cdc2/<B>CyclinB> B activation in the presence of replicating nuclear DNA. This role for Ran is mediated through control of the tyrosine phosphorylation state of Cdc2 and appears to Be distinct from other effects on nuclear import, nuclear formation and DNA replication. When extracts were supplemented with RCC1 protein prior to addition of Ran T24N, inhiBition of Cdc2/<B>CyclinB> B By Ran T24N was relieved. This suggests that Ran T24N may act in a dominant manner By sequestering RCC1 in an inactive form. In contrast to Ran T24N, a mutant of Ran (Q69L) defective in GTPase activity and hence locked in the GTP-Bound state has no inhiBitory effect on Cdc2/<B>CyclinB> B activation. In the light of these results, we propose that generation of the GTP-Bound form of Ran is required for Cdc2/<B>CyclinB> B activation and entry into mitosis when this process is coupled to the progression of S-phase.
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Regulation of Cdc2/<B>CyclinB> B activation By Ran, a Ras-related GTPase.
Journal of cell science, 1995Co-Authors: P R Clarke, C Klebe, A Wittinghofer, E KarsentiAbstract:During the cell cycle, a checkpoint prevents the initiation of mitosis until S-phase is completed. The molecular mechanism may involve the RCC1 protein, which catalyses guanine nucleotide exchange on the Ras-related nuclear protein, Ran (or TC4). Genetic studies have suggested that RCC1 may Be involved in sensing the replication state of DNA and controlling the activation of Cdc2/<B>CyclinB> B protein kinase through Ran. In this report, we present direct Biochemical evidence for the post-translational control of Cdc2/<B>CyclinB> B activation By Ran. In a cell-free system of concentrated Xenopus egg extracts supplemented with nuclei, a mutant form of Ran (T24N) analogous to dominant inactive mutants of other Ras-related GTPases inhiBits Cdc2/<B>CyclinB> B activation in the presence of replicating nuclear DNA. This role for Ran is mediated through control of the tyrosine phosphorylation state of Cdc2 and appears to Be distinct from other effects on nuclear import, nuclear formation and DNA replication. When extracts were supplemented with RCC1 protein prior to addition of Ran T24N, inhiBition of Cdc2/<B>CyclinB> B By Ran T24N was relieved. This suggests that Ran T24N may act in a dominant manner By sequestering RCC1 in an inactive form. In contrast to Ran T24N, a mutant of Ran (Q69L) defective in GTPase activity and hence locked in the GTP-Bound state has no inhiBitory effect on Cdc2/<B>CyclinB> B activation. In the light of these results, we propose that generation of the GTP-Bound form of Ran is required for Cdc2/<B>CyclinB> B activation and entry into mitosis when this process is coupled to the progression of S-phase.
Sandrine Boulben - One of the best experts on this subject based on the ideXlab platform.
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<B>CyclinB> B Translation Depends on mTOR Activity after Fertilization in Sea Urchin EmBryos
PloS one, 2016Co-Authors: Héloïse Chassé, Odile Mulner-lorillon, Sandrine Boulben, Virginie Glippa, Julia Morales, Patrick CormierAbstract:The <B>CyclinB> B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhiBitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls <B>CyclinB> B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhiBits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhiBits gloBal protein synthesis, delays <B>CyclinB> B accumulation, <B>CyclinB> B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered By fertilization. PP242 inhiBits <B>CyclinB> B mRNA recruitment into active polysomes triggered By fertilization. An amount of <B>CyclinB> B mRNA present in active polysomes appears to Be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, <B>CyclinB> B mRNA translation is controlled By two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism.
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pesticide roundup provokes cell division dysfunction at the level of cdk1 <B>CyclinB> B activation
Chemical Research in Toxicology, 2002Co-Authors: Julie Marc, Sandrine Boulben, Dorothee Hureau, Gaël Durand, Odile Mulnerlorillon, Robert BelléAbstract:To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin emBryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin emBryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could Be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a suBthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy Between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/<B>CyclinB> B regulates universally the M-phase of the cell cycle, we analyzed CDK1/<B>CyclinB> B activation during the first division of early development. Roundup delayed the activation of CDK1/<B>CyclinB> B in vivo. Roundup inhiBited also the gloBal protein synthetic rate without preventing the accumulation of <B>CyclinB> B. In summary, Roundup affects cell cycle regulation By delaying activation of the CDK1/<B>CyclinB> B complex, By synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/<B>CyclinB> B regulator, our results question the safety of glyphosate and Roundup on human health.
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Pesticide Roundup provokes cell division dysfunction at the level of CDK1/<B>CyclinB> B activation.
Chemical research in toxicology, 2002Co-Authors: Julie Marc, Odile Mulner-lorillon, Sandrine Boulben, Dorothee Hureau, Gaël Durand, Robert BelléAbstract:To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin emBryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin emBryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could Be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a suBthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy Between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/<B>CyclinB> B regulates universally the M-phase of the cell cycle, we analyzed CDK1/<B>CyclinB> B activation during the first division of early development. Roundup delayed the activation of CDK1/<B>CyclinB> B in vivo. Roundup inhiBited also the gloBal protein synthetic rate without preventing the accumulation of <B>CyclinB> B. In summary, Roundup affects cell cycle regulation By delaying activation of the CDK1/<B>CyclinB> B complex, By synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/<B>CyclinB> B regulator, our results question the safety of glyphosate and Roundup on human health.
