Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

Lorne J. Hofseth, Shin'ichi Saito, S. Perwez Hussain, Michael G. Espey, Katrina M. Miranda, Yuzuru Araki, Chamelli Jhappan, Yuichiro Higashimoto, Peijun He, Steven P. Linke, Martha M. Quezado, Irit Zurer, Varda Rotter, David A. Wink, Ettore Appella, Curtis C. Harris

Research output: Contribution to journalArticlepeer-review

298 Scopus citations


Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 post-translational modifications, leading to an increase in p53 transcriptional targets and a G2/M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21WAF1 was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation.

Original languageEnglish (US)
Pages (from-to)143-148
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 7 2003


  • Phosphorylation
  • Posttranslational modification

ASJC Scopus subject areas

  • General


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