| Literature DB >> 12518062 |
Lorne J Hofseth1, 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.
Abstract
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 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G(2)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 p21(WAF1) 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.Entities:
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Year: 2002 PMID： 12518062 PMCID： PMC140909 DOI： 10.1073/pnas.0237083100
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205