Loss of Cdc20 causes a securin-dependent metaphase arrest in two-cell mouse embryos.
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.
Li
Min
M
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
York
J Philippe
JP
Zhang
Pumin
P
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008677:Metaphase; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064249:Securin; D008941:Spindle Apparatus / Q000378:metabolism
D002352:Carrier Proteins; D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D064249:Securin