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Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis

Lindsey A Allan1, Paul R Clarke

  • 1Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.

Molecular Cell
|May 1, 2007
PubMed

Insights

Cellular damage triggers cell cycle arrest or apoptosis. Caspase-9 phosphorylation restrains apoptosis during mitosis, controlling cell death sensitivity to antimitotic drugs.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genomics

Background:

  • Metazoan cells prevent genomic instability via cell cycle arrest or apoptosis.
  • The molecular regulation balancing these responses remains unclear.

Purpose of the Study:

  • Investigate the cell cycle regulation of apoptosis.
  • Elucidate the role of caspase-9 in mitotic cell death decisions.

Main Methods:

  • RNA interference (RNAi) to study caspase-9 function.
  • Analysis of caspase-9 phosphorylation at Thr125.
  • Utilizing CDK1/cyclin B1 and microtubule poisons.

Main Results:

  • Caspase-9 is periodically phosphorylated at inhibitory site Thr125 by CDK1/cyclin B1 during mitosis.
  • This phosphorylation restrains apoptosis from mitosis.
  • Nonphosphorylatable caspase-9 mutants enhance apoptosis induction by antimitotic drugs.

Conclusions:

  • Phosphorylation of caspase-9 at Thr125 regulates the intrinsic apoptotic pathway threshold.
  • This mechanism restrains apoptosis during mitosis and influences sensitivity to antimitotic agents.

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