The spindle checkpoint requires cyclin-dependent kinase activity

  1. Vincenzo D'Angiolella1,
  2. Cecilia Mari2,
  3. Donatella Nocera3,
  4. Linda Rametti3, and
  5. Domenico Grieco1,2,4
  1. 1 Dipartimento di Biologia e Patologia Molecolare e Cellulare L., Califano Medical School, University of Napoli, Federico II, Pansini 5, 80131 Napoli, Italy
  2. 2 Facolta' di Scienze Biotecnologiche, University of Napoli, Federico II, Pansini 5, 80131 Napoli, Italy
  3. 3 Dipartimento di Medicina Sperimentale, G. Salvatore, Medical School, University of Catanzaro, T. Campanella, 88100 Cantanzaro, Italy

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

Footnotes

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.267603.

  • ↵4 Corresponding author. E-MAIL grido{at}unicz.it; FAX 39-081-7463252.

    • Accepted August 8, 2003.
    • Received April 10, 2003.
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This Article

  1. doi: 10.1101/gad.267603 Genes & Dev. 17: 2520-2525 Cold Spring Harbor Laboratory Press

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