Abstract
We have investigated the influence of p53 on radiation-induced G2 cell cycle arrest using human H1299 cells expressing temperature-sensitive p53. Gamma-irradiated cells lacking p53 arrested transiently in G2 with Cdc2 extensively phosphorylated at the inhibitory sites Thr14 and Tyr15, and with both Cdc2 and cyclin B1 restricted to the cytoplasm. Activation of p53 by temperature shift resulted in a more protracted G2 arrest that could not be overridden by checkpoint-abrogating drugs. Surprisingly, this enhancement of G2 arrest was associated with a marked lack of inhibitory phosphorylation of Cdc2 and with the nuclear localization of both Cdc2 and cyclin B1. While transient expression of an A14F15 mutant form of Cdc2 that is not subject to inhibitory phosphorylation induced mitotic catastrophe in cells lacking p53, the p53-expressing cells were relatively refractory to this effect. Enforced expression of p21WAF1/CIP1 was sufficient to confer nuclear localization on Cdc2 in the p53 null cells, though immunodepletion experiments demonstrated that only a small proportion of Cdc2 was stably associated with p21WAF1/CIP1 in the p53-expressing cells. We conclude that a p53-dependent pathway can operate after exposure of human cells to ionising radiation to promote G2 arrest accompanied by nuclear translocation rather than inhibitory phosphorylation of Cdc2.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Winters, Z., Ongkeko, W., Harris, A. et al. p53 regulates Cdc2 independently of inhibitory phosphorylation to reinforce radiation-induced G2 arrest in human cells. Oncogene 17, 673–684 (1998). https://doi.org/10.1038/sj.onc.1201991
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201991
Keywords
This article is cited by
-
The live cell DNA stain SiR-Hoechst induces DNA damage responses and impairs cell cycle progression
Scientific Reports (2018)
-
KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα
Oncogene (2009)
-
Cell growth inhibition, G2M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803
Investigational New Drugs (2007)
-
Diallyl trisulfide-induced G2–M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc25C
Oncogene (2005)
-
Cytoplasmic p21 WAF1/CIP1 expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis
Breast Cancer Research (2003)