Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis

Steven D. Leach, Caroline D. Scatena, Christopher J. Keefer, Holly A. Goodman, Si Young Song, Liying Yang, Jennifer A. Pietenpol

Research output: Contribution to journalArticlepeer-review

Abstract

The G2 cell cycle checkpoint protects cells from potentially lethal mitotic entry after DNA damage. This checkpoint involves inhibitory phosphorylation of Cdc2 at the tyrosine-15 (Y15) position, mediated in part by the Wee1 protein kinase. Recent evidence suggests that p53 may accelerate mitotic entry after DNA damage and that the override of the G2 checkpoint may play a role in the induction of apoptosis by p53. To determine the biochemical mechanism by which p53 inactivates the G2 checkpoint, the effects of p53 activation on Wee1 expression, Cdc2-Y15 phosphorylation, and cyclin B1-associated Cdc2 kinase activity were examined. Under conditions of either growth arrest or apoptosis, p53 activation resulted in the down- regulation of Wee1 expression and dephosphorylation of Cdc2. A parallel increase in cyclin B1/Cdc2 kinase activity was observed during p53-mediated apoptosis. Negative regulation of the Wee1 expression and Cdc2 phosphorylation by p53 was also evident in thymus tissue from p53(+/+) mice but not from p53(-/-) mice. Inactivation of the G2 checkpoint may contribute to the tumor suppressor activity of p53.

Original languageEnglish (US)
Pages (from-to)3231-3236
Number of pages6
JournalCancer Research
Volume58
Issue number15
StatePublished - Aug 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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