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Induction of a G2-phase arrest in Xenopus egg extracts by activation of p42 mitogen-activated protein kinase

S A Walter1, T M Guadagno, J E Ferrell

  • 1Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305-5332, USA.

Molecular Biology of the Cell
|November 15, 1997
PubMed

Insights

Activation of the mitogen-activated protein (MAP) kinase cascade can induce a G2-phase arrest in Xenopus extracts. This novel mechanism prevents cell cycle progression by inhibiting Cdc2/cyclin complex activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Mitogen-activated protein (MAP) kinase cascade activation is known to regulate cell cycle progression.
  • Previous studies show MAP kinase activation can cause G2-phase release or mitotic arrest in Xenopus oocytes and extracts.

Purpose of the Study:

  • To investigate the role of MAP kinase cascade activation in regulating interphase arrest in cycling Xenopus extracts.
  • To elucidate the molecular mechanisms underlying MAP kinase-induced cell cycle arrest.

Main Methods:

  • Utilized cycling Xenopus egg extracts.
  • Activated the MAP kinase cascade at different cell cycle stages.
  • Analyzed nuclear envelope status, chromatin condensation, H1 kinase activity, DNA replication, cyclin synthesis, and protein phosphorylation (Cdc25, Wee1).

Main Results:

  • Early MAP kinase cascade activation induced an interphase (G2-like) arrest characterized by an intact nuclear envelope and inhibited Cdc2/cyclin complex activation.
  • Late activation (before mitosis) resulted in a mitotic arrest.
  • The G2 arrest was independent of the DNA replication checkpoint and Cdk2/cyclin E.
  • Delayed MAP kinase inactivation prolonged the G2-phase in the first mitotic cycle after fertilization.

Conclusions:

  • MAP kinase cascade activation can induce a novel G2-phase arrest in cycling extracts.
  • This arrest mechanism involves preventing the activation of Cdc2/cyclin complexes.
  • Persistent MAP kinase activity after fertilization may explain the G2-phase in the first mitotic cell cycle.

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