Loss of Cdc20 Causes a Securin-Dependent Metaphase Arrest in Two-Cell Mouse Embryos
- 1 May 2007
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 27 (9) , 3481-3488
- https://doi.org/10.1128/mcb.02088-06
Abstract
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase mediating targeted proteolysis through ubiquitination of protein substrates to control the progression of mitosis. The APC/C recognizes its substrates through two adapter proteins, Cdc20 and Cdh1, which contain similar C-terminal domains composed of seven WD-40 repeats believed to be involved in interacting with their substrates. During the transition from metaphase to anaphase, APC/C-Cdc20 mediates the ubiquitination of securin and cyclin B1, allowing the activation of separase and the onset of anaphase and mitotic exit. APC/C-Cdc20 and APC/C-Cdh1 have overlapping substrates. It is unclear whether they are redundant for mitosis. Using a gene-trapping approach, we have obtained mice which lack Cdc20 function. These mice show failed embryogenesis. The embryos were arrested in metaphase at the two-cell stage with high levels of cyclin B1, indicating an essential role of Cdc20 in mitosis that is not redundant with that of Cdh1. Interestingly, Cdc20 and securin double mutant embryos could not maintain the metaphase arrest, suggesting a role of securin in preventing mitotic exit.Keywords
This publication has 31 references indexed in Scilit:
- Securin and Separase Phosphorylation Act Redundantly to Maintain Sister Chromatid Cohesion in Mammalian CellsMolecular Biology of the Cell, 2005
- Mutual Inhibition of Separase and Cdk1 by Two-Step Complex FormationMolecular Cell, 2005
- Degradation of Cyclin B Is Required for the Onset of Anaphase in Mammalian CellsJournal of Biological Chemistry, 2003
- The anaphase-promoting complex: it's not just for mitosis any moreGenes & Development, 2002
- Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1The Journal of cell biology, 2002
- A System for Stable Expression of Short Interfering RNAs in Mammalian CellsScience, 2002
- The KEN box regulates Clb2 proteolysis in G1 and at the metaphase-to-anaphase transitionCurrent Biology, 2001
- Cohesin Cleavage by Separase Required for Anaphase and Cytokinesis in Human CellsScience, 2001
- Separation anxiety at the centromereTrends in Cell Biology, 2000
- Control of mitotic transitions by the anaphase–promoting complexPhilosophical Transactions Of The Royal Society B-Biological Sciences, 1999