Aurora B regulates MCAK at the mitotic centromere

Paul D. Andrews, Yulia Ovechkina, Nick Morrice, Michael Wagenbach, Karen Duncan, Linda Wordeman, Jason R. Swedlow

    Research output: Contribution to journalArticlepeer-review

    400 Citations (Scopus)

    Abstract

    Chromosome orientation and alignment within the mitotic spindle requires the Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK). Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's microtubule depolymerizing activity in vitro, and phospho-mimic (S/E) mutants of MCAK inhibited depolymerization in vivo. Expression of either MCAK (S/E) or MCAK (S/A) mutants increased the frequency of syntelic microtubule-kinetochore attachments and mono-oriented chromosomes. MCAK phosphorylation also regulates MCAK localization: the MCAK (S/E) mutant frequently localized to the inner centromere while the (S/A) mutant concentrated at kinetochores. We also detected two different binding sites for MCAK using FRAP analysis of the different MCAK mutants. Moreover, disruption of Aurora B function by expression of a kinase-dead mutant or RNAi prevented centromeric targeting of MCAK. These results link Aurora B activity to MCAK function, with Aurora B regulating MCAK's activity and its localization at the centromere and kinetochore.
    Original languageEnglish
    Pages (from-to)253-268
    Number of pages16
    JournalDevelopmental Cell
    Volume6
    Issue number2
    DOIs
    Publication statusPublished - 2004

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