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 journalArticle

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
Externally publishedYes

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Cyclin B1
Phosphorylation
Apoptosis
DNA Damage
Phosphotransferases
Growth
G2 Phase Cell Cycle Checkpoints
Protein Kinases
Thymus Gland
Tyrosine
Down-Regulation
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Leach, S. D., Scatena, C. D., Keefer, C. J., Goodman, H. A., Song, S. Y., Yang, L., & Pietenpol, J. A. (1998). Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis. Cancer Research, 58(15), 3231-3236.

Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis. / Leach, Steven D.; Scatena, Caroline D.; Keefer, Christopher J.; Goodman, Holly A.; Song, Si Young; Yang, Liying; Pietenpol, Jennifer A.

In: Cancer Research, Vol. 58, No. 15, 01.08.1998, p. 3231-3236.

Research output: Contribution to journalArticle

Leach, SD, Scatena, CD, Keefer, CJ, Goodman, HA, Song, SY, Yang, L & Pietenpol, JA 1998, 'Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis', Cancer Research, vol. 58, no. 15, pp. 3231-3236.
Leach SD, Scatena CD, Keefer CJ, Goodman HA, Song SY, Yang L et al. Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis. Cancer Research. 1998 Aug 1;58(15):3231-3236.
Leach, Steven D. ; Scatena, Caroline D. ; Keefer, Christopher J. ; Goodman, Holly A. ; Song, Si Young ; Yang, Liying ; Pietenpol, Jennifer A. / Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis. In: Cancer Research. 1998 ; Vol. 58, No. 15. pp. 3231-3236.
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