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Cited by 46Microtubule and mitosis dynamicsCancer Treatment and PharmacologySynthesis and biological activity

Regulatory mechanisms that control mitotic kinesins

Open access
Yount, Amber L., Zong, Hailing, Walczak, Claire E.·2015·Experimental Cell Research
DOI 10.1016/j.yexcr.2014.12.015PMC PMC4433799
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Abstract

During mitosis, the mitotic spindle is assembled to align chromosomes at the spindle equator in metaphase, and to separate the genetic material equally to daughter cells in anaphase. The spindle itself is a macromolecular machine composed of an array of dynamic microtubules and associated proteins that coordinate the diverse events of mitosis. Among the microtubule associated proteins are a plethora of molecular motor proteins that couple the energy of ATP hydrolysis to force production. These motors, including members of the kinesin superfamily, must function at the right time and in the right place to insure the fidelity of mitosis. Misregulation of mitotic motors in disease states, such as cancer, underlies their potential utility as targets for antitumor drug development and highlights the importance of understanding the molecular mechanisms for regulating their function. Here, we focus on recent progress about regulatory mechanisms that control the proper function of mitotic kinesins and highlight new findings that lay the path for future studies.

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Crossref · 10.1016/j.yexcr.2014.12.015

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

32 of 68 cited sources checked · 16 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In vivo, the Kinesin-4 Kif4 is essential for targeting PRC1 to the central spindle.

    “In vivo, the Kinesin-4, Kif4, is essential for targeting PRC1 to the central spindle [23]; however, elegant in vitro reconstitution experiments have demonstrated that PRC1 and XKlp1 (another Kinesin-4) coordinately regulate central spindle assembly by interacting specifically in regions of anti-parallel MT overlap and controlling the dynamics of the plus-ends of central spindle microtubules [24].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [23] Kurasawa, 2004, Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation, EMBO J. source

      The Results state that PRC1 still binds central-spindle microtubules in KIF4-deficient cells, where it remains dispersed. KIF4 is required to concentrate PRC1 at the spindle midline, not to target it to the central spindle. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Binding of one or more mitosis-specific transcription factors, such as FOXM1, can promote expression of many cell cycle regulated genes at the G2/M transition.

    “For example, binding of one or more mitosis-specific transcription factors, such as FOXM1, can promote expression of many cell cycle regulated genes at the G2/M transition [1].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Alvarez-Fernandez, 2013, Novel functions of FoxM1: from molecular mechanisms to cancer therapy, Front. Oncol. source
  • Premisecitation

    DREAM/MMB complexes regulate genes that control kinesin expression.

    “Other important transcriptional networks controlling kinesin expression include those genes regulated by the DREAM/MMB (Myb-MuvB) complexes [3].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Sadasivam, 2013, The DREAM complex: master coordinator of cell cycle-dependent gene expression, Nat. Rev. Cancer source

      The Conclusions and perspectives section says DREAM and BMYB–MuvB regulate cell-cycle-dependent gene expression. Our copy does not identify kinesin expression or kinesin-related genes as targets of these complexes (searched: kinesin, motor proteins, KIF), so the kinesin-specific part is unsupported. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Premisecitation

    The Ran-GTP gradient regulates spindle assembly factors through binding to the nuclear transport receptors importin alpha and beta.

    “The canonical example of spatial regulation by gradients in mitosis is illustrated by the Ran-GTP gradient, which regulates spindle assembly factors (SAFs) through binding to the nuclear transport receptors importin alpha and beta.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Kalab, 2008, The RanGTP gradient—a GPS for the mitotic spindle, J. Cell Sci. source

      The Introduction explains that RanGTP binding to importin β releases spindle assembly factors from importins, regulating their activity near chromatin (page unavailable). It identifies importin α as an adaptor through which importin β associates with cargos, but does not support the claim that RanGTP binds directly to both importin α and β. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    During mitosis, nuclear transport receptors are involved directly in spatial control via the Ran-GTP gradient.

    “However, during mitosis the nuclear transport receptors are also involved directly in spatial control via the Ran-GTP gradient [8].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Kalab, 2008, The RanGTP gradient—a GPS for the mitotic spindle, J. Cell Sci. source
  • May combine two claims. 39
  • Classified as probably not a substantial claim. 4
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    The Ran gradient is found primarily around chromosomes and extends toward the spindle poles.

    “The Ran gradient is found primarily around chromosomes and extends toward the spindle poles [8].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [8] Kalab, 2008, The RanGTP gradient—a GPS for the mitotic spindle, J. Cell Sci. source

  • May combine two claims.

    Premisecitation

    The DREAM/MMB complex is a multi-subunit complex with repressive subunits that inhibit gene expression during G1/S and activating subunits that stimulate expression during G2/M.

    “This is a multi-subunit complex that associates with repressive subunits, which inhibit gene expression during G1/S, and with activating subunits, which stimulate gene expression during G2/M.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Sadasivam, 2013, The DREAM complex: master coordinator of cell cycle-dependent gene expression, Nat. Rev. Cancer source

      The sections on mammalian DREAM and BMYB–MuvB complexes and on their switch support a multi-subunit MuvB core that associates with repressive factors or with factors promoting late cell-cycle expression. But the paper places DREAM-mediated repression in quiescent G0 cells, not during G1/S; it says genes repressed in G0 are expressed at the G1/S transition. Page numbers are not available in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Kid uses binding to importins for its initial localization to chromatin but is also dependent upon Ran-GTP for continued association with chromosomes.

    “Kid uses the binding to importins for its initial localization to chromatin but is also dependent upon Ran-GTP for continued association with chromosomes [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Tahara, 2008, Importin-beta and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid, J. Cell Biol. source

      The Results section on Ran-GTP–mediated chromosome loading says that importin-α/β initially targets hKid to chromosomes and that local Ran-GTP promotes its loading and accumulation. It does not establish that Ran-GTP is required for hKid’s continued association once bound; the Results also report weak chromosome binding under Ran-independent conditions. Page numbers were not available in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Mutation in the EB binding domain results in a deficiency in targeting to the microtubule plus end and a corresponding decrease in microtubule depolymerization activity for both Kif18B and MCAK.

    “Mutation in the EB binding domain results in a deficiency in targeting to the microtubule plus end and a corresponding decrease in microtubule depolymerization activity for both Kif18B and MCAK [15, 16], suggesting that EB binding is functionally important for these motors.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [15] Tanenbaum, 2011, A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases, Curr. Biol. source
    • cites [16] Montenegro Gouveia, 2010, In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends, Curr. Biol. source

  • May combine two claims.

    Premisecitation

    Motor binding to EBs is primarily regulated through an SxIP motif within the kinesin sequence and has been shown for Kinesin-5s (Eg5), Kinesin-8s (Kif18B), and Kinesin-13s (MCAK).

    “Motor binding to EBs is primarily regulated through an SxIP motif within the kinesin sequence and has been shown for Kinesin-5s (Eg5), Kinesin-8s (Kif18B), and Kinesin-13s (MCAK) [13–17].”
    Quote in the paperNot a substantial claim2 of 5 sources checked
    • cites [13] Honnappa, 2009, An EB1-binding motif acts as a microtubule tip localization signal, Cell source
    • cites [14] Stout, 2011, Kif18B interacts with EB1 and controls astral microtubule length during mitosis, Mol. Biol. Cell source

      The Results section (‘Kif18B interacts with EB1 to target to astral MT ends’; page unavailable) demonstrates direct binding between Kif18B and EB1. It also explicitly says Kif18B lacks the consensus SxIP sequence, so this paper does not support attributing that binding to an SxIP motif. The cited passages do not establish the claim about Eg5 or MCAK. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [15] Tanenbaum, 2011, A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases, Curr. Biol. source
    • cites [16] Montenegro Gouveia, 2010, In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends, Curr. Biol. source
    • cites [17] Jiang, 2012, A proteome-wide screen for mammalian SxIP motif-containing microtubule plus-end tracking proteins, Curr. Biol. source

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Newer proteomics approaches are identifying novel protein-protein interactions and putative sites of phosphoregulation and other post-translational modifications, which should provide a complete roadmap of the mitotic spindle.

    “In addition, newer proteomics approaches are identifying novel protein-protein interactions and putative sites of phosphoregulation and other post-translational modifications, which should provide a complete roadmap of the mitotic spindle [61, 62].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [61] Syred, 2013, Cell cycle regulation of microtubule interactomes: multi-layered regulation is critical for the interphase/mitosis transition, Mol. Cell. Proteomics source

      The Results report phosphorylation-site measurements, and the Experimental Procedures describe mapping an interaction network for identified microtubule-associated proteins. But the Discussion says other modifications were not actively maintained and notes that the method missed proteins binding exclusively to dynamic microtubule ends. The paper therefore supports proteomics as a way to build a broader picture, not the claim that it should provide a complete roadmap of the mitotic spindle. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [62] Maliga, 2013, A genomic toolkit to investigate kinesin and myosin motor function in cells, Nat. Cell Biol. source

  • May combine two claims.

    Premisecitation

    Both the Ran-GTP and Aurora B/CPC pathways contribute to spindle assembly.

    “While it is known that both pathways contribute to spindle assembly [60], their local concentrations and activation could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [60] Maresca, 2009, Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity, Curr. Biol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The local concentrations and activation of Ran-GTP and Aurora B/CPC could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.

    “While it is known that both pathways contribute to spindle assembly [60], their local concentrations and activation could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [60] Maresca, 2009, Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity, Curr. Biol. source

  • May combine two claims.

    Premisecitation

    MCAK phosphorylation by Aurora A within its C-terminus regulates its association with spindle poles and contributes to Ran-regulated spindle bipolarity.

    “Additionally, MCAK phosphorylation by Aurora A within its C-terminus regulates its association with spindle poles and contributes to Ran-regulated spindle bipolarity [33].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [33] Zhang, 2008, Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity, Mol. Biol. Cell source

  • May combine two claims.

    Premisecitation

    Adjacent to T422 is a docking motif for type 1 phosphatase PP1γ, which blocks direct binding of Aurora kinases and allows Cenp-E to deliver PP1 to kinetochores, where it helps contribute to stable bi-orientation of chromosomes.

    “Adjacent to T422 is a docking motif for type 1 phosphatase (PP1γ), which blocks the direct binding of Aurora kinases and allows Cenp-E to deliver PP1 to kinetochores, where it also helps contribute to the stable bi-orientation of chromosomes [53].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [53] Kim, 2010, Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E, Cell source

      The Results identify a PP1 docking motif overlapping T422, and the Introduction says CENP-E delivers PP1 to the outer kinetochore for stable biorientation. But the binding mechanism is reversed: the Results show that Aurora-mediated phosphorylation disrupts PP1 binding to CENP-E, not that the PP1 docking motif blocks direct binding of Aurora kinases. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Eg5 is a plus-end directed motor with two motor dimers oriented in an anti-parallel fashion and a pair of motor domains on either end.

    “The Kinesin-5, Eg5, is a plus-end directed motor that has two motor dimers oriented in an anti-parallel fashion with a pair of motor domains (heads) on either end (Fig. 2A) [38].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] Kashina, 1996, A bipolar kinesin, Nature source

      The paper’s Abstract describes a model in which two KRP130 dimers form a bipolar tetramer with two motor domains at each end, and proposes that it walks toward microtubule plus ends. Its experiments concern KRP130, an Eg5 relative; they do not directly establish Eg5’s structure or plus-end-directed movement as facts. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Kinesin-5 and Kinesin-14 proteins play antagonistic roles in spindle length control, and this antagonism can be recapitulated in vitro.

    “Given that Kinesin-5 and Kinesin-14 proteins play antagonistic roles in spindle length control and that this antagonism can be recapitulated in vitro [45, 46], this system will be ideal to begin to look at the integration of motor activity and regulation in more complex motor ensembles.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [45] Hentrich, 2010, Microtubule organization by the antagonistic mitotic motors kinesin-5 and kinesin-14, J. Cell Biol. source
    • cites [46] Tao, 2006, A homotetrameric kinesin-5, KLP61F, bundles microtubules and antagonizes Ncd in motility assays, Curr. Biol. source

  • May combine two claims.

    Premisecitation

    Eg5 utilizes ATP-independent diffusion when it binds to single microtubules, whereas binding to a second microtubule activates ATP hydrolysis activity and switches Eg5 from diffusive to directed movement.

    “Eg5 utilizes ATP-independent diffusion when it binds to single microtubules, whereas binding to a second microtubule activates ATP hydrolysis activity and switches Eg5 from diffusive to directed movement [40].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [40] Kapitein, 2008, Microtubule cross-linking triggers the directional motility of kinesin-5, J. Cell Biol. source

      In Results and discussion (page not available), the paper reports ATP-independent diffusion on single microtubules at near-physiological ionic strength and a switch to directional motility upon binding a second microtubule. It says directional motility requires ATP hydrolysis and suggests that ATP-dependent motility is activated by the second microtubule, but it does not establish that binding directly activates ATP hydrolysis activity. The claim also omits the ionic-strength qualification: Eg5 can move directionally on a single microtubule at lower ionic strength. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Eg5 possesses another microtubule binding site in its tail that enhances motor processivity, microtubule association, and microtubule crosslinking.

    “Furthermore, it was shown that Eg5 possesses another microtubule binding site in its tail that enhances motor processivity, microtubule association, and microtubule crosslinking [41], but it is still unknown how microtubule-binding events regulate the motor activity.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [41] Weinger, 2011, A nonmotor microtubule binding site in kinesin-5 is required for filament crosslinking and sliding, Curr. Biol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    FOXM1 is aberrantly expressed in many cancers and could contribute to the upregulation of kinesins seen in cancer cells.

    “This is interesting because FOXM1 is aberrantly expressed in many cancers and could contribute to the upregulation of kinesins seen in cancer cells [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] F. Kozielski (Ed.), Kinesins in Cancer, Springer, 2015 in press. source
    • Rests on an assumption: Misregulation of mitotic motors in disease states such as cancer underlies their potential utility as targets for antitumor drug development.

  • May combine two claims.

    Premisecitation

    Kid is a plus-end directed kinesin localized to chromosome arms that contributes to chromosome congression by mediating the polar ejection force.

    “Kid is a plus-end directed kinesin that is localized to chromosome arms and contributes to chromosome congression by mediating the polar ejection force [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Vanneste, 2011, Chromokinesins: localization-dependent functions and regulation during cell division, Biochem. Soc. Trans. source

  • May combine two claims.

    Premisecitation

    For Kinesin-14s, Ran regulation is important for regulating microtubule cross-linking activity, and expression of NLS mutants results in aberrant microtubule cross-linking in interphase.

    “For the Kinesin-14s, this Ran regulation is important to regulate the microtubule cross-linking activity of the protein [10], and expression of NLS mutants results in aberrant microtubule cross-linking in interphase [7].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Ems-McClung, 2004, Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal, Mol. Biol. Cell source
    • cites [7] Cai, 2009, Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules, Mol. Biol. Cell source

  • May combine two claims.

    Premisereasoning

    Disruption of HURP results in defects in chromatin-mediated spindle assembly, suggesting that the effects of HURP are not limited to K-fiber associated motors.

    “Disruption of HURP results in defects in chromatin-mediated spindle assembly, suggesting that the effects of HURP are not limited to K-fiber associated motors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    The CPC targets chromosome arms early in mitosis, focuses at the inner centromere during prometaphase and metaphase, and is left behind in the spindle midzone during anaphase and telophase.

    “The CPC targets to chromosome arms early in mitosis, focuses at the inner centromere during prometaphase and metaphase and then is left behind in the spindle midzone during anaphase and telophase.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Interpretationcitation

    HURP localization is Ran-dependent, suggesting that the Ran gradient is a master control system that modulates the localization of many spindle motors directly and indirectly by regulating other spindle MAPs.

    “To highlight the complexity of these mitotic localization networks, HURP localization is also Ran-dependent [19], suggesting that the Ran gradient is a master control system that modulates”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Sillje, 2006, HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes, Curr. Biol. source

  • May combine two claims.

    Premisenone given

    Kinesins localize by directly binding to subsets of microtubules, to kinetochores, or to chromosomes.

    “Kinesins accomplish this task by directly binding to subsets of microtubules, to kinetochores, or to chromosomes.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Kinesins must be localized properly to complete their intended functions.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The DREAM/MMB complex is highly integrated with the p53 control network, and p53 is mutated in a large number of cancers.

    “The DREAM/MMB complex is also highly integrated with the p53 control network, and p53 is mutated in a large number of cancers, highlighting the importance of the”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Expression of a nondegradable Cin8p does not perturb cell cycle progression, but there is a small increase in the percentage of mitotic cells with abnormal spindles.

    “Although expression of a nondegradable Cin8p does not perturb cell cycle progression, there was a small increase in the percentage of mitotic cells with abnormal spindles [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Hildebrandt, 2001, Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence, Mol. Biol. Cell source

  • May combine two claims.

    Premisecitation

    Expression of mutant forms of HSET during interphase leads to excessive microtubule bundling and cellular toxicity.

    “The consequences of failing to degrade HSET have not been examined, although expression of mutant forms of HSET during interphase leads to excessive microtubule bundling and cellular toxicity [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Cai, 2009, Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules, Mol. Biol. Cell source

  • May combine two claims.

    Premisecitation

    The phenotypes of TPX2 disruption and HURP disruption are similar, but they appear to act in independent pathways during spindle formation, suggesting that the HURP complex is not constitutively active.

    “However, while the phenotypes of TPX2 disruption and HURP disruption are similar, they appear to act in independent pathways during spindle formation, suggesting that the HURP complex is not constitutively active [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Casanova, 2008, Hepatoma up-regulated protein is required for chromatin-induced microtubule assembly independently of TPX2, Mol. Biol. Cell source

  • May combine two claims.

    Premisecitation

    Overexpression of a HURP fragment that prevents Kif18A plus end localization leads to decreased association of Kif18A and an increased amplitude of kinetochore oscillations, ultimately delaying chromosome congression similar to the phenotype of Kif18A knockdown.

    “Overexpression of a HURP fragment that prevents Kif18A plus end localization leads to decreased association of Kif18A and an increased amplitude of kinetochore oscillations [18], ultimately leading to a delay in chromosome congression, similar to the phenotype of Kif18A knockdown.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Ye, 2011, HURP regulates chromosome congression by modulating kinesin Kif18A function, Curr. Biol. source

  • May combine two claims.

    Premisecitation

    PRC1 is essential for central spindle assembly through its recruitment of the Kinesin-6 proteins MKLP-1 and MKLP-2, which are both essential for cytokinesis.

    “PRC1 is essential for central spindle assembly through its recruitment of the Kinesin-6 proteins MKLP-1 and MKLP-2, which are both essential for cytokinesis [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Douglas, 2010, Still entangled: assembly of the central spindle by multiple microtubule modulators, Semin. Cell Dev. Biol. source

  • May combine two claims.

    Interpretationnone given

    Distinct temporal and spatial regulatory mechanisms can affect the same motors at different points in the cell cycle and different motors at the same point in the cell cycle.

    “These distinct temporal and spatial regulatory mechanisms can affect the same motors at different points in the cell cycle and different motors at the same point in the cell cycle.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Aurora-B dependent phosphorylation is physiologically important in error correction, as phosphorylated MCAK is enriched at merotelically attached kinetochores.

    “Aurora-B dependent phosphorylation is physiologically important in error correction, as phosphorylated MCAK is enriched at merotelically attached kinetochores [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Knowlton, 2006, Aurora B is enriched at merotelic attachment sites, where it regulates MCAK, Curr. Biol. source

  • May combine two claims.

    Interpretationreasoning

    Kid is regulated spatially and temporally by the Ran-GTP gradient, phosphorylation, and protein-protein interaction, providing an example of how the cell uses multiple mechanisms to ensure precise localization of mitotic motors to sub-spindle structures.

    “Thus, Kid is regulated spatially and temporally by the Ran-GTP gradient, phosphorylation, and protein-protein interaction providing an example of how the cell uses multiple mechanisms to ensure the precise localization of mitotic motors to sub-spindle structures.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Phosphorylation of PRC1 by Cdk1 prevents its association with the spindle until late mitosis, when dephosphorylated PRC1 binds to the spindle and recruits Kinesin-6 proteins.

    “Phosphorylation of PRC1 by Cdk1 prevents its association with the spindle until late mitosis when dephosphorylated PRC1 binds to the spindle and recruits Kinesin-6 proteins [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Douglas, 2010, Still entangled: assembly of the central spindle by multiple microtubule modulators, Semin. Cell Dev. Biol. source

  • May combine two claims.

    Premisecitation

    The spatial localization of Kid is controlled by Cdk1 phosphorylation, which regulates the binding affinity of Kid to microtubules and influences the pool of available Kid to bind to chromosome arms.

    “The spatial localization of Kid is also controlled by Cdk1 phosphorylation, which regulates the binding affinity of Kid to microtubules, which in turn influences the pool of available Kid to bind to chromosome arms [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Ohsugi, 2003, Cdc2-mediated phosphorylation of Kid controls its distribution to spindle and chromosomes, EMBO J. source

  • May combine two claims.

    Premisenone given

    Aurora A gradient emanates from the spindle poles whereas Aurora B and PP1γ are primarily localized at the kinetochores.

    “These activities are also spatially controlled because an Aurora A gradient emanates from the spindle poles whereas Aurora B and PP1γ are primarily localized at the kinetochores.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Multi-kinase regulation has been demonstrated for MCAK, Eg5, and MKLP-1, suggesting that this is likely a common mechanism of action.

    “Multi-kinase regulation has also been demonstrated for MCAK, Eg5, and MKLP-1, suggesting that this is likely a common mechanism of action.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Aurora B phosphorylation at S196 changes MCAK from a closed to open conformation, resulting in a decrease in MCAK affinity for the microtubule that contributes to reduced microtubule depolymerization activity.

    “However, this regulation is more complex because it was shown that Aurora B phosphorylation at S196 changes MCAK from a closed to open conformation, which results in a decrease in MCAK affinity for the microtubule that contributes to reduced microtubule depolymerization activity [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Ems-McClung, 2013, Aurora B inhibits MCAK activity through a phosphoconformational switch that reduces microtubule association, Curr. Biol. source

  • May combine two claims.

    Premisecitation

    In early mitosis, Aurora A phosphorylation of Kif2a inhibits its enzymatic activity and decreases the targeting of Kif2a on spindle microtubules, allowing stabilization of the minus ends of microtubules emanating from the chromatin.

    “In early mitosis, as the spindle starts to form, Aurora A phosphorylation of Kif2a inhibits its enzymatic activity and decreases the targeting of Kif2a on spindle microtubules, which allows for stabilization of the minus ends of microtubules that are emanating from the chromatin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Like Eg5, Kinesin-14s are activated by microtubule cross-linking to slide anti-parallel microtubules, but they tether parallel microtubules.

    “Like Eg5, the Kinesin-14s are activated by microtubule cross-linking [43] to slide anti-parallel microtubules, but they tether parallel microtubules [44].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [43] Furuta, 2008, Minus-end-directed motor Ncd exhibits processive movement that is enhanced by microtubule bundling in vitro, Curr. Biol. source
    • cites [44] Fink, 2009, The mitotic kinesin-14 Ncd drives directional microtubule–microtubule sliding, Nat. Cell Biol. source

  • May combine two claims.

    Interpretationreasoning

    This allows Eg5 to slide microtubules only when it is actively engaged in microtubule cross-links, which contributes to spindle pole separation.

    “This allows Eg5 to only slide microtubules when it is actively engaged in microtubule cross-links, which contributes to spindle pole separation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In vitro reconstitution experiments demonstrated that PRC1 and XKlp1 coordinately regulate central spindle assembly by interacting specifically in regions of anti-parallel microtubule overlap and controlling the dynamics of the plus-ends of central spindle microtubules.

    “In vivo, the Kinesin-4, Kif4, is essential for targeting PRC1 to the central spindle [23]; however, elegant in vitro reconstitution experiments have demonstrated that PRC1 and XKlp1 (another Kinesin-4) coordinately regulate central spindle assembly by interacting specifically in regions of anti-parallel MT overlap and controlling the dynamics of the plus-ends of central spindle microtubules [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Bieling, 2010, A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps, Cell source

  • May combine two claims.

    Premisereasoning

    Phosphorylation of the Cenp-E tail by either MPS1 or Cdk1 reverses the autoinhibition, providing a mechanism to activate Cenp-E motility during early mitosis when it is needed for chromosome congression.

    “Phosphorylation of the tail by either MPS1-or Cdk1- reverses the autoinhibition, which provides a mechanism to activate Cenp-E motility during early mitosis when it is needed for chromosome congression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Aurora B positively influences MCAK localization to centromeres by phosphorylating S110 in its kinetochore-targeting domain, whereas phosphorylation at T95 promotes association with chromosome arms.

    “Aurora B positively influences MCAK localization to centromeres by phosphorylating S110 in its kinetochore-targeting domain, whereas phosphorylation at T95 promotes association with chromosome arms.”
    Quote in the paperNot a substantial claim
41 of 41

  • The paper relies on this without support.

    Misregulation of mitotic motors in disease states such as cancer underlies their potential utility as targets for antitumor drug development.

    “Misregulation of mitotic motors in disease states, such as cancer, underlies their potential utility as targets for antitumor drug development and highlights the importance of understanding the molecular mechanisms for regulating their function.”

  • The paper relies on this without support.

    Mitotic motors must function at the right time and in the right place to ensure the fidelity of mitosis.

    “These motors, including members of the kinesin superfamily, must function at the right time and in the right place to insure the fidelity of mitosis.”

  • The paper relies on this without support.

    Kinesins must be localized properly to complete their intended functions.

    “The localization of mitotic kinesins can be as diverse as their functions, but the two go hand-in-hand because kinesins must be localized properly to complete their intended functions.”

  • The paper relies on this without support.

    Ensuring that the activities of mitotic motors are precisely tuned is an important regulatory mechanism.

    “While the proper expression and physical localization of mitotic kinesins are essential for mitosis, ensuring that the activities of motors are precisely tuned is also an important regulatory mechanism.”
4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Wood, 1997, CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment, Cell, 91, 357, 10.1016/S0092-8674(00)80419-5 · DOI · Paper page
  2. Jang, 2009, Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a, J. Cell Sci., 122, 1334, 10.1242/jcs.044321 · DOI · Paper page

Cited by

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Related

Authors
Yount, A. L., Zong, H., & Walczak, C. E.
Affiliations
Indiana University Bloomington (US)
Corresponding author
Walczak, Claire E.
ORCID
Walczak, Claire E.
Venue
Experimental Cell Research
Publisher
Elsevier BV
Published
2015-05
Volume
334
Issue
1
Pages
70-77
ISSN
0014-4827 (ISSN-L)
DOI
10.1016/j.yexcr.2014.12.015
PMC
PMC4433799
OpenAlex
W2047380283
Semantic Scholar
6b416ca80010c1984e0fd7494ff854e89fe1006c
Cited by
39
References
60
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 1
FWCI
0.43
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Cell Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (R01GM059618)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
mitotic kinesin, kinesin superfamily, mitotic spindle, mitosis regulation, microtubule-associated proteins, molecular motors, cancer, antitumor drug targets, chromosome segregation
MeSH terms
Humans, Mitosis, Kinesins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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