Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function

Xin Zhang, Weijie Lan, Stephanie C. Ems-McClung, P. Todd Stukenberg, Claire E. Walczak

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Chromosome congression and segregation require the proper attachment of microtubules to the two sister kinetochores. Disruption of either Aurora B kinase or the Kinesin-13 mitotic centromere-associated feinesin (MCAK) increases chromosome misalignment and missegregation due to improper kinetochore- microtubule attachments. MCAK localization and activity are regulated by Aurora B, but how Aurora B phosphorylation of MCAK affects spindle assembly is unclear. Here, we show that the binding of MCAK to chromosome arms is also regulated by Aurora B and that Aurora B-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. MCAK association with chromosome arms is promoted by phosphorylation of T95 on MCAK, whereas phosphorylation of S196 on MCAK promotes dissociation from the arms. Although targeting of MCAK to centromeres requires phosphorylation of S110 on MCAK, dephosphorylation of T95 on MCAK increases the binding of MCAK to centromeres. Our study reveals a new role for Aurora B, which is to prevent excess MCAK binding to chromatin to facilitate chromatin-nucleated spindle assembly. Our study also shows that the interplay between multiple phosphorylation sites of MCAK may be critical to temporally and spatially control MCAK function.

Original languageEnglish (US)
Pages (from-to)3264-3276
Number of pages13
JournalMolecular Biology of the Cell
Volume18
Issue number9
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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