Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules

Horst, Armando van der; Vromans, Martijn J.M.; Bouwman, Kim M.; Waal, Maike S. van der; Hadders, Michael A.; Lens, Susanne M.A.

doi:10.1016/j.celrep.2015.06.038

Cited by 50 publications

(55 citation statements)

References 32 publications

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“…We confirmed this finding by using the Haspin kinase inhibitor 5-ITu, similar to previous observations for Borealin in 5-ITu–treated cells (Bekier et al, 2015). This pool of Aurora B persists in the presence of the spindle poison nocodazole, ruling out the involvement of CPC binding to microtubules (Banerjee et al, 2014; Fink et al, 2017; Samejima et al, 2015; van der Horst et al, 2015; Wheelock et al, 2017). We presented several lines of evidence indicating that H2ApT120-bound Sgo1 provides the docking site for Aurora B at the KT-proximal centromere.…”

Section: Discussionmentioning

confidence: 98%

Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

Cai

Zhang

Chen

et al. 2019

Journal of Cell Biology

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Aurora B kinase plays an essential role in chromosome bi-orientation, which is a prerequisite for equal segregation of chromosomes during mitosis. However, it remains largely unclear whether centromere-localized Aurora B is required for faithful chromosome segregation. Here we show that histone H3 Thr-3 phosphorylation (H3pT3) and H2A Thr-120 phosphorylation (H2ApT120) can independently recruit Aurora B. Disrupting H3pT3-mediated localization of Aurora B at the inner centromere impedes the decline in H2ApT120 during metaphase and causes H2ApT120-dependent accumulation of Aurora B at the kinetochore-proximal centromere. Consequently, silencing of the spindle assembly checkpoint (SAC) is delayed, whereas the fidelity of chromosome segregation is negligibly affected. Further eliminating an H2ApT120-dependent pool of Aurora B restores proper timing for SAC silencing but increases chromosome missegregation. Our data indicate that H2ApT120-mediated localization of Aurora B compensates for the loss of an H3pT3-dependent pool of Aurora B to correct improper kinetochore–microtubule attachments. This study provides important insights into how centromeric Aurora B regulates SAC and kinetochore attachment to microtubules to ensure error-free chromosome segregation.

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Section: Discussionmentioning

confidence: 98%

Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

Cai

Zhang

Chen

et al. 2019

Journal of Cell Biology

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“…LacI-GFP, LacI-GFP-Haspin, LacI-GFP-Haspin kinase dead (K511A), LacI-GFP-Bub1, LacI-GFP-Bub1 E252K , LacI-GFP-Bub1 E252K kinase dead (D946A), Sgo1-LacI-GFP, or LacI-GFP-Sgo2 was cloned into pAceBac1-CMV or pAceBac1-Ubc (van der Horst et al, 2015). Bacmids were generated using the Bac-to-Bac system in conjunction with EMBacY cells (Berger et al, 2004; Bieniossek et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Hadders

Hindriksen

Truong

et al. 2020

Journal of Cell Biology

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Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase–dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT–MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B–dependent kinetochore phosphorylation.

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“…4B). Whereas CEP192, by docking -TuRC, serves as a centrosomal anchor for the minus ends of growing MTs (47), INCENP functions during mitosis at the interface between chromatin and spindle MTs by virtue of being targeted to these structures through its centromere-targeting domain that binds Survivin and Borealin and two MT-binding domains, respectively (141,161,(179)(180)(181). The dual recognition of chromatin and MTs is essential for AurB activation, spindle assembly, and robust spindle assembly checkpoint arrest (161,181,182).…”

Section: The Cep192 Complex and The Cpc As Signaling Hubs At Oppositementioning

confidence: 99%

Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis

Joukov¹,

2018

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Mitosis is controlled by reversible protein phosphorylation involving specific kinases and phosphatases. A handful of major mitotic protein kinases, such as the cyclin B-CDK1 complex, the Aurora kinases, and Polo-like kinase 1 (PLK1), cooperatively regulate distinct mitotic processes. Research has identified proteins and mechanisms that integrate these kinases into signaling cascades that guide essential mitotic events. These findings have important implications for our understanding of the mechanisms of mitotic regulation and may advance the development of novel antimitotic drugs. We review collected evidence that in vertebrates, the Aurora kinases serve as catalytic subunits of distinct complexes formed with the four scaffold proteins Bora, CEP192, INCENP, and TPX2, which we deem "core" Aurora cofactors. These complexes and the Aurora-PLK1 cascades organized by Bora, CEP192, and INCENP control crucial aspects of mitosis and all pathways of spindle assembly. We compare the mechanisms of Aurora activation in relation to the different spindle assembly pathways and draw a functional analogy between the CEP192 complex and the chromosomal passenger complex that may reflect the coevolution of centrosomes, kinetochores, and the actomyosin cleavage apparatus. We also analyze the roles and mechanisms of Aurora-PLK1 signaling in the cell and centrosome cycles and in the DNA damage response.

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Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules

Cited by 50 publications

References 32 publications

Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis

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