The interrelationship between APC/C and Plk1 activities in centriole disengagement

Department of Cell Biology, University of Massachusetts Medical School , Worcester, MA 01605 , USA.
Biology Open (Impact Factor: 2.42). 11/2012; 1(11):1153-60. DOI: 10.1242/bio.20122626
Source: PubMed


Mother-daughter centriole disengagement, the necessary first step in centriole duplication, involves Plk1 activity in early mitosis and separase activity after APC/C activity mediates securin degradation. Plk1 activity is thought to be essential and sufficient for centriole disengagement with separase activity playing a supporting but non-essential role. In separase null cells, however, centriole disengagement is substantially delayed. The ability of APC/C activity alone to mediate centriole disengagement has not been directly tested. We investigate the interrelationship between Plk1 and APC/C activities in disengaging centrioles in S or G2 HeLa and RPE1 cells, cell types that do not reduplicate centrioles when arrested in S phase. Knockdown of the interphase APC/C inhibitor Emi1 leads to centriole disengagement and reduplication of the mother centrioles, though this is slow. Strong inhibition of Plk1 activity, if any, during S does not block centriole disengagement and mother centriole reduplication in Emi1 depleted cells. Centriole disengagement depends on APC/C-Cdh1 activity, not APC/C-Cdc20 activity. Also, Plk1 and APC/C-Cdh1 activities can independently promote centriole disengagement in G2 arrested cells. Thus, Plk1 and APC/C-Cdh1 activities are independent but slow pathways for centriole disengagement. By having two slow mechanisms for disengagement working together, the cell ensures that centrioles will not prematurely separate in late G2 or early mitosis, thereby risking multipolar spindle assembly, but rather disengage in a timely fashion only late in mitosis.

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    • "Inhibition of Plk1 in a Xenopus CSF extract, for example, will block disengagement in the presence of separase (Schockel et al. 2011), and overexpression of Plk1 will promote centriole disengagement in G 2 (Loncarek et al. 2010). It also seems that APC/C activity contributes to disengagement (Prosser et al. 2012), and that Plk1 and APC/ C-Cdh1 activities can independently achieve this (Hatano and Sluder 2012). The duality of the regulation of sister chromatid separation and centriole disengagement is echoed in the suggestion of a role for Plk1 in localizing the small isoform of Shugoshin1 (sSgo1). "
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