title: Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit.
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/C(Fzr) 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.
authors: Cell Cycle Development Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: Francesco
authors: F
authors: Meghini
authors: Cell Cycle Development Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: Torcato
authors: 0000-0002-9359-7111
authors: T
authors: Martins
authors: Cell Cycle Development Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.|Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: Xavier
authors: X
authors: Tait
authors: Cell Cycle Control Group, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
authors: Kazuyuki
authors: K
authors: Fujimitsu
authors: Cell Cycle Control Group, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
authors: Hiroyuki
authors: H
authors: Yamano
authors: Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: David M
authors: DM
authors: Glover
authors: Cell Cycle Development Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: Yuu
authors: 0000-0001-6223-1320
authors: Y
authors: Kimata
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism; D064200:Cdh1 Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D013997:Time Factors; D003598:Cytoskeletal Proteins
chemical_list: D064096:Aurora Kinase A; D064200:Cdh1 Proteins; D029721:Drosophila Proteins; C529373:SPD-2 protein, Drosophila; D003598:Cytoskeletal Proteins; C577674:fzr protein, Drosophila; C576942:aurA protein, Drosophila