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Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis
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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. doi:10.1016/j.cub.2010.03.055 ISSN 0960-9822.
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Official URL: http://dx.doi.org/10.1016/j.cub.2010.03.055
Abstract
Centralspindlin is essential for the formation of microtubule bundle structures and the equatorial recruitment of factors critical for cytokinesis [ [1] and [2]]. Stable accumulation of centralspindlin at the spindle midzone requires its multimerization into clusters [3] and Aurora B kinase activity [ [4], [5], [6], [7], [8], [9] and [10]], which peaks at the central spindle during anaphase [ [11] and [12]]. Although Aurora B phosphorylates centralspindlin directly [ [13], [14], [15], [16] and [17]], 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 | ||||
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Subjects: | R Medicine > R Medicine (General) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Current Biology | ||||
Publisher: | Cell Press | ||||
ISSN: | 0960-9822 | ||||
Official Date: | 25 May 2010 | ||||
Dates: |
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Volume: | Vol.20 | ||||
Number: | No.10 | ||||
Page Range: | pp. 927-933 | ||||
DOI: | 10.1016/j.cub.2010.03.055 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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