Abstract
Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase activity and the E3 ubiquitin ligase SCF-βTrCP. Here, we show that Plk1 is also required for the timely destruction of its activator Aurora A in late anaphase. It has been shown that Aurora A destruction is controlled by the auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C). Remarkably, we found that Plk1-depletion prevented the efficient dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1, at least in part, through direct phosphorylation of the human phosphatase Cdc14A, controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A.
Highlights
The transition from G2 to mitosis is triggered by rapid activation of the Cyclin B1/Cdk1-complex [1]
To determine Anaphase-Promoting Complex/Cyclosome (APC/C) activation in Polo-like kinase 1 (Plk1)-depleted cells, we first followed the destruction of a GFP-tagged N-terminal fragment of Cyclin B1 [39]
Very similar kinetics of GFP-Cyclin B1-NT degradation were observed in monastrol-treated cells (Fig. 1B and 1D) and Plk1-depleted cells, which shows that Plk1 does not influence APC/C-Cdc20 activity in checkpoint-compromised cells (Fig. 1)
Summary
The transition from G2 to mitosis is triggered by rapid activation of the Cyclin B1/Cdk1-complex [1]. Polo-like kinase 1 (Plk1) positively influences mitotic entry by activating the Cdk1activating Cdc phosphatases and by inducing the ubiquitindependent destruction of the Cdk1-repressor Wee1 [2,3]. In addition to targeting Wee for destruction, re-activation of Plk reinitiates the cell cycle and promotes mitotic entry by destabilizing Claspin, an adaptor protein required for Chk1-activation [7,8,9]. Plk further controls the b-TrCP-dependent destruction of the APC/C-inhibitor Emi-1 and the mitotic regulator Bora [10,11,12,13,14]. Plk exerts many of its effects on the G2/M transition by promoting the timely destruction of critical cell cycle regulators
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