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Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit

Francesco Meghini, Torcato Martins, Xavier Tait, Kazuyuki Fujimitsu, Hiroyuki Yamano, David M. Glover and Yuu Kimata ()
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Francesco Meghini: Cell Cycle Development Group, University of Cambridge
Torcato Martins: Cell Cycle Development Group, University of Cambridge
Xavier Tait: Cell Cycle Development Group, University of Cambridge
Kazuyuki Fujimitsu: Cell Cycle Control Group, UCL Cancer Institute, University College London
Hiroyuki Yamano: Cell Cycle Control Group, UCL Cancer Institute, University College London
David M. Glover: Cell Cycle Genetics Group, University of Cambridge
Yuu Kimata: Cell Cycle Development Group, University of Cambridge

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila. The localization of Fzr to the centriole during interphase depends on direct interaction with Spd2. By generating Spd2 mutants unable to bind Fzr, we show that centrosomal localization of Fzr is essential for optimal APC/C activation towards its centrosomal substrate Aurora A. Finally, we show that Spd2 is also a novel APC/CFzr substrate. Our study is the first to demonstrate the critical importance of distinct subcellular pools of APC/C activators in the spatiotemporal control of APC/C activity.

Date: 2016
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DOI: 10.1038/ncomms12607

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