Abstract
The p21WAF1/CIP1/SDI1 gene is an important regulator of crucial cellular processes, including cell cycle control, cellular differentiation, and the response to genotoxic stress. Induction of p21 gene expression upon DNA damage is widely believed to be p53-dependent. In the present study we analysed the expression of p21 following genotoxic stress, using different DNA-damaging agents and cellular systems. We found that the p21 response markedly varied between different cell lines and also for different genotoxic agents within the same cell line. Genotoxic induction of p21 mRNA expression can occur in the presence of p53-antagonists, such as overexpressed mdm-2 or human papillomavirus (HPV) E6, and in cells harbouring mutated p53 genes. Moreover, upon genotoxic stress, p21 mRNA and protein expression were found to be uncoupled in several cell lines. Thus, transcriptional and postranscriptional changes in p21 expression following DNA damage are not necessarily linked to the intracellular p53 status but strongly depend on the individual cellular background and the type of DNA-damaging agent. Our findings indicate that p21 expression following genotoxic stress underlies a complex control and can be substantially modulated on the posttranscriptional level in a cell-specific manner.
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
Butz, K., Geisen, C., Ullmann, A. et al. Uncoupling of p21WAF1/CIP1/SDI1 mRNA and protein expression upon genotoxic stress. Oncogene 17, 781–787 (1998). https://doi.org/10.1038/sj.onc.1201995
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201995
Keywords
This article is cited by
-
Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses
Journal of Molecular Medicine (2007)
-
Low p21Waf1/Cip1 protein level sensitizes testicular germ cell tumor cells to Fas-mediated apoptosis
Oncogene (2004)
-
siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells
Oncogene (2003)
-
Cell cycle regulatory protein expression in fresh acute myeloid leukemia cells and after drug exposure
Leukemia (2001)
-
HPV-18 E6*I protein modulates the E6-directed degradation of p53 by binding to full-length HPV-18 E6
Oncogene (1999)