The spindle checkpoint requires cyclin-dependent kinase activity
Open Access
- 15 October 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (20) , 2520-2525
- https://doi.org/10.1101/gad.267603
Abstract
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.Keywords
This publication has 24 references indexed in Scilit:
- Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpointNature Cell Biology, 2003
- Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggsGenes & Development, 2003
- Distinct Cell Cycle Timing Requirements for Extracellular Signal-Regulated Kinase and Phosphoinositide 3-Kinase Signaling Pathways in Somatic Cell MitosisMolecular and Cellular Biology, 2002
- The Anaphase-Promoting ComplexMolecular Cell, 2002
- Waiting for AnaphaseCell, 2000
- Specificity and mechanism of action of some commonly used protein kinase inhibitorsBiochemical Journal, 2000
- Phosphorylation of Cdc20/Fizzy Negatively Regulates the Mammalian Cyclosome/APC in the Mitotic CheckpointBiochemical and Biophysical Research Communications, 2000
- Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein p23Science, 1996
- A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extractsCell, 1994
- Association of human cyclin E with a periodic G1-S phase protein kinaseScience, 1992