APC/C Cdh1 targets aurora kinase to control reorganization of the mitotic spindle at anaphase

Curr Biol. 2008 Nov 11;18(21):1649-58. doi: 10.1016/j.cub.2008.09.058. Epub 2008 Oct 30.

Abstract

Background: Control of mitotic cell cycles by the anaphase-promoting complex or cyclosome (APC/C) ubiquitin ligase depends on its coactivators Cdc20 and Cdh1. APC/C(Cdc20) is active during mitosis and promotes anaphase onset by targeting mitotic cyclins and securin. APC/C(Cdh1) becomes active during mitotic exit and has essential targets in G1 phase. It is not known whether targeting of substrates by APC/C(Cdh1) plays any role in the final stages of mitosis. Here, we have investigated the role of APC/C(Cdh1) at this time in the cell cycle by using siRNA-mediated depletion of Cdh1 in human cells.

Results: In 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/C(Cdh1) 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.

Conclusions: Targeting of Aurora kinases at anaphase by APC/C(Cdh1) participates in the control of mitotic exit and cytokinesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase*
  • Anaphase-Promoting Complex-Cyclosome
  • Antigens, CD
  • Aurora Kinases
  • Cadherins / metabolism*
  • Cdc20 Proteins
  • Cell Cycle Proteins / metabolism
  • Cytokinesis
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Spindle Apparatus / metabolism*
  • Time Factors
  • Ubiquitin-Protein Ligase Complexes / metabolism*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • RNA, Small Interfering
  • CDC20 protein, human
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases