APC/CCdh1 Targets Aurora Kinase to Control Reorganization of the Mitotic Spindle at Anaphase

SummaryBackgroundControl of mitotic cell cycles by the anaphase-promoting complex or cyclosome (APC/C) ubiquitin ligase depends on its coactivators Cdc20 and Cdh1. APC/CCdc20 is active during mitosis and promotes anaphase onset by targeting mitotic cyclins and securin. APC/CCdh1 becomes active during mitotic exit and has essential targets in G1 phase. It is not known whether targeting of substrates by APC/CCdh1 plays any role in the final stages of mitosis. Here, we have investigated the role of APC/CCdh1 at this time in the cell cycle by using siRNA-mediated depletion of Cdh1 in human cells.ResultsIn contrast to the current view that Cdh1 takes over from Cdc20 at anaphase, we show that reduced Cdh1 levels have no effect on destruction of many APC/C substrates during mitotic exit but strongly and specifically stabilize Aurora kinases. We find that APC/CCdh1 is required for assembly of a robust spindle midzone at anaphase and for normal timings of spindle elongation and cytokinesis. The effect of Cdh1 siRNA on anaphase spindle dynamics requires Aurora A, and its effect can be mimicked by nondegradable Aurora kinase.ConclusionsTargeting of Aurora kinases at anaphase by APC/CCdh1 participates in the control of mitotic exit and cytokinesis.