Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes.
| Autor: | Ballmer D; Department of Biochemistry, University of Oxford, Oxford, UK.; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK., Lou HJ; Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA., Ishii M; Department of Biochemistry, University of Oxford, Oxford, UK.; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK., Turk BE; Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA., Akiyoshi B; Department of Biochemistry, University of Oxford, Oxford, UK.; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of cell biology [J Cell Biol] 2024 Nov 04; Vol. 223 (11). Date of Electronic Publication: 2024 Aug 28. |
| DOI: | 10.1083/jcb.202401169 |
| Abstrakt: | Kinetochores form the interface between chromosomes and spindle microtubules and are thus under tight control by a complex regulatory circuitry. The Aurora B kinase plays a central role within this circuitry by destabilizing improper kinetochore-microtubule attachments and relaying the attachment status to the spindle assembly checkpoint. Intriguingly, Aurora B is conserved even in kinetoplastids, a group of early-branching eukaryotes which possess a unique set of kinetochore proteins. It remains unclear how their kinetochores are regulated to ensure faithful chromosome segregation. Here, we show in Trypanosoma brucei that Aurora B activity controls the metaphase-to-anaphase transition through phosphorylation of the divergent Bub1-like protein KKT14. Depletion of KKT14 overrides the metaphase arrest resulting from Aurora B inhibition, while expression of non-phosphorylatable KKT14 delays anaphase onset. Finally, we demonstrate that re-targeting Aurora B to the outer kinetochore suffices to promote mitotic exit but causes extensive chromosome missegregation in anaphase. Our results indicate that Aurora B and KKT14 are involved in an unconventional circuitry controlling cell cycle progression in trypanosomes. (© 2024 Ballmer et al.) |
| Databáze: | MEDLINE |
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