Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin

Hanley, Mariah L.; Yoo, Tae Yeon; Sonnett, Matthew; Needleman, Daniel; Mitchison, Timothy J.

doi:10.1091/mbc.e16-12-0860

Cited by 13 publications

(11 citation statements)

References 87 publications

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“…We also compared the diffusion rates of CPC components inside coacervates in vitro and at inner centromeres using fluorescence correlation spectroscopy (FCS). GFP-borealin dynamics in both the cytoplasm and the inner centromere is best described by a two-populations model (slow diffusing population, D slow = 0.1-1 μm 2 s −1 ; fast diffusing population, D fast = 10-15 μm 2 s −1 ) as previously reported 28,29 ( Supplementary Fig. 3a-e).…”

Section: Resultssupporting

confidence: 64%

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex

et al. 2019

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The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere.

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Section: Resultssupporting

confidence: 64%

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex

et al. 2019

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“…This is conceivably via the known ubiquitin-dependent regulators of Aurora B function at chromatin (Dobrynin et al, 2011;Krupina et al, 2016;Ramadan et al, 2007). Other work shows that inactive cytoplasmic CPC is chaperoned by the nucleoplasmin family proteins (Hanley et al, 2017), suggesting that this might inhibit binding to other factors such as MKLP2 away from chromatin. The data presented here may indicate an additional possibility, that the N terminus of INCENP contains a regulatory element.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle

Serena

Bastos

Elliott

et al. 2020

Journal of Cell Biology

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The Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase.

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“…3B) (156)(157)(158). Furthermore, the T-loop phosphorylation of both AurA and AurB is normally suppressed by protein phosphatases and molecular chaperones, and this suppression is released upon oligomerization of CEP192 complexes or CPCs, respectively (39,40,109,112,159). Finally, the active Aurora kinase in CEP192 complexes and CPCs promotes MT assembly, albeit through distinct mechanisms specific for the centrosomedriven and kinetochore-driven pathways, respectively.…”

Section: Aurora-plk1 Modules At Distinct Mitotic Signaling Platformsmentioning

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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Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin

Cited by 13 publications

References 87 publications

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex

Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle

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

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