Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis
Douglas, Max E., Davies, Tim, Joseph, Nimesh and Mishima, Masanori. (2010) Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis. Current Biology, Vol.20 (No.10). pp. 927-933. ISSN 0960-9822Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.cub.2010.03.055
Centralspindlin is essential for the formation of microtubule bundle structures and the equatorial recruitment of factors critical for cytokinesis [  and ]. Stable accumulation of centralspindlin at the spindle midzone requires its multimerization into clusters  and Aurora B kinase activity [ , , , , ,  and ], which peaks at the central spindle during anaphase [  and ]. Although Aurora B phosphorylates centralspindlin directly [ , , ,  and ], how this regulates centralspindlin localization is unknown. Here we identify a novel regulatory mechanism by which Aurora B enables centralspindlin to accumulate stably at the spindle midzone. We show that 14-3-3 protein binds centralspindlin when the kinesin-6 component MKLP1 is phosphorylated at S710. 14-3-3 prevents centralspindlin from clustering in vitro, and an MKLP1 mutant that is unable to bind 14-3-3 forms aberrant clusters in vivo. Interestingly, 14-3-3 binding is inhibited by phosphorylation of S708, a known Aurora B target site that lies within the motif bound by 14-3-3. S708 phosphorylation is required for MKLP1 to stably localize to the central spindle, but it is dispensable in an MKLP1 mutant that does not bind 14-3-3. We propose that 14-3-3 serves as a global inhibitor of centralspindlin that allows Aurora B to locally activate clustering and the stable accumulation of centralspindlin between segregating chromosomes.
|Item Type:||Journal Article|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School > Biomedical Cell Biology
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Current Biology|
|Date:||25 May 2010|
|Page Range:||pp. 927-933|
|Access rights to Published version:||Restricted or Subscription Access|
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