Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression

Vukušić, Kruno; Tolić, Iva M. (2025) Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression. Nature Communications, 16 (1). ISSN 2041-1723

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Abstract

Chromosome congression is crucial for accurate cell division, with key roles played by kinetochore components, the molecular motor CENP-E/kinesin-7, and Aurora B kinase. However, Aurora B kinase can both inhibit and promote congression, suggesting the presence of a larger signaling network. Our study demonstrates that centrosomes inhibit congression initiation when CENP-E is inactive by regulating the activity of kinetochore components. Depletion of centrioles via Plk4 kinase inhibition allows chromosomes near acentriolar poles to initiate congression independently of CENP-E. At centriolar poles, high Aurora A kinase enhances Aurora B activity, increasing phosphorylation of microtubule-binding proteins at kinetochores and preventing stable microtubule attachments in the absence of CENP-E. Conversely, inhibition of Aurora A or expression of a dephosphorylatable mutant of the kinetochore microtubule-binding protein Hec1 enables congression initiation without CENP-E. We propose a negative feedback mechanism involving Aurora kinases and CENP-E that regulates the timing of chromosome movement by modulating kinetochore–microtubule attachments and fibrous corona expansion, with the Aurora A activity gradient providing critical spatial cues for the network’s function.

Item Type:	Article
Uncontrolled Keywords:	cell-cycle arrest; microtubule; attachment; inhibitor; instability; stability; protein
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molecular origins of aneuploidies in healthy and diseased human tissues-ANEUPLOIDY Iva Tolić; Nenad Pavin 855158 EK Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomedicini-IPSted Iva Tolić KK.01.1.1.04.0057 EK Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri-QuantiXLie Hrvoje Buljan; Pavle Pandžić; Vit Tuček; Tomislav Marketin KK.01.1.1.01.0004 EK
Depositing User:	Iva Marija Tolić
Date Deposited:	07 Jan 2026 13:49
URI:	http://fulir.irb.hr/id/eprint/10739
DOI:	10.1038/s41467-025-64804-1

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