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 language | English (US) |
|---|---|
| Pages (from-to) | 3231-3236 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 58 |
| Issue number | 15 |
| State | Published - Aug 1 1998 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Negative regulation of wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis
AU - Leach, Steven D.
AU - Scatena, Caroline D.
AU - Keefer, Christopher J.
AU - Goodman, Holly A.
AU - Song, Si Young
AU - Yang, Liying
AU - Pietenpol, Jennifer A.
PY - 1998/8/1
Y1 - 1998/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032145479&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032145479&partnerID=8YFLogxK
M3 - Article
C2 - 9699647
AN - SCOPUS:0032145479
VL - 58
SP - 3231
EP - 3236
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 15
ER -