Abstract
Treatment of mouse (12)1/CA cells with adriamycin or irradiation with U.V.C. induces p53-dependent transcription of a β-galactosidase reporter and the endogenous p21/Waf1/Cip1 gene. Despite the induction of Waf1, the cells arrest only transiently in G1 or G2, then resume growth and eventually undergo apoptosis. In situ analysis of β-galactosidase activity in U.V.C.-irradiated cells revealed a much higher level of p53-dependent transcription in cells undergoing apoptosis compared to transiently arrested cells. Incubation of the treated cells with salicylate, which inhibits the activation of protein kinases and transcription factors involved in stress responses, inhibits both p53-dependent transcription and apoptosis. The inhibition of transcription is due mainly to impairment of the ability of p53 to bind to DNA. The treated cells resume their p53-dependent programs whenever the salicylate is removed, even after as long as 60 h after the DNA has been damaged. Therefore, the p53-activating signals generated by adriamycin or U.V.C. are very long lived. The resumption of p53-dependent transcription is not accompanied by additional accumulation of the p53 protein, indicating that the activation of p53 is regulated by a separate pathway.
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
Chernov, M., Stark, G. The p53 activation and apoptosis induced by DNA damage are reversibly inhibited by salicylate. Oncogene 14, 2503–2510 (1997). https://doi.org/10.1038/sj.onc.1201104
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201104
Keywords
This article is cited by
-
11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes
Journal of Cancer Research and Clinical Oncology (2016)
-
By the grace of peeling: the brace function of the stratum corneum in the protection from photo-induced keratinocyte carcinogenesis
Archives of Dermatological Research (2008)
-
Chemical Peeling by SA-PEG Remodels Photo-damaged Skin: Suppressing p53 Expression and Normalizing Keratinocyte Differentiation
Journal of Investigative Dermatology (2006)
-
Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53
Cell Death & Differentiation (2006)
-
Salicylate Protects Hearing and Kidney Function from Cisplatin Toxicity without Compromising its Oncolytic Action
Laboratory Investigation (2002)