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/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.

NEK7 is required for G1 progression and procentriole formation

“…, 2012; Sonnen et al. , 2012), which is consistent with a recent study on Drosophila Cdh1/FZR1 (Meghini et al. , 2016).…”

APC/C Cdh1 -Rock2 pathway controls dendritic integrity and memory

“…Because the APC/C Cdh1 recognition motif, the KEN box, is conserved both in Rock1 and Rock2, we next aimed to resolve this apparent paradox. In cancer cells, Rock1 is present in the cytosol and Rock2 both in the nucleus and cytosol (23,24); however, APC is present only in the nucleus (25,26).…”

The E3 ubiquitin ligase APC / C C dh1 degrades MCPH 1 after MCPH1‐βTr CP 2‐Cdc25A‐mediated mitotic entry to ensure neurogenesis

“…APC/C is another ubiquitin E3 ligase complex, which has two activators, Cdc20 and Cdh1. While APC/C Cdc20 plays a role in the early phase of mitosis and in metaphase/anaphase transition, APC/C Cdh1 is activated in the mitotic exit and the early G1 phase to ensure G1 phase progression and to prevent S‐phase entry (van Leuken et al , ; Meghini et al , ). It is also shown that a deletion of Cdh1 delays neurogenesis (van Leuken et al , ; Delgado‐Esteban et al , ).…”