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The spindle checkpoint prevents anaphase onset until completion of mitotic spindle assembly by restraining activation of the ubiquitin ligase anaphase-promoting complex/cyclosome-Cdc20 (APC/CCdc20). We show that the spindle checkpoint requires mitotic cyclin-dependent kinase (cdk) activity. Inhibiting cdk activity overrides checkpoint-dependent arrest in Xenopus egg extracts and human cells. Following inhibition, the interaction between APC/C and Cdc20 transiently increases while the inhibitory checkpoint protein Mad2 dissociates from Cdc20. Cdk inhibition also overcomes Mad2-induced mitotic arrest. In addition, in vitro cdk1-phosphorylated Cdc20 interacts with Mad2 rather than APC/ C. Thus, cdk activity is required to restrain APC/CCdc20 activation until completion of spindle assembly.

Original publication




Journal article


Genes Dev

Publication Date





2520 - 2525


Anaphase-Promoting Complex-Cyclosome, Animals, Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome, Cdc20 Proteins, Cell Cycle Proteins, Cyclin-Dependent Kinases, HeLa Cells, Humans, Ligases, Ovum, Spindle Apparatus, Ubiquitin-Protein Ligase Complexes, Xenopus