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Biochem Biophys Res Commun. 2005 Mar 25;328(4):1107-12.

COX-2 regulates p53 activity and inhibits DNA damage-induced apoptosis.

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  • 1Department of Biochemistry and Molecular Biology, Kangwon National University College of Medicine, Chuncheon 200-701, Republic of Korea.

Abstract

We have previously shown that p53 induces cyclooxygenase-2 (COX-2) expression and COX-2 inhibits p53- or genotoxic stress-induced apoptosis. However, the COX-2 effects have been demonstrated indirectly by the use of a selective inhibitor, NS-398, and the molecular mechanisms by which COX-2 inhibits apoptosis have not been identified. In the present study, we demonstrated that COX-2 inhibits genotoxic stress-induced apoptosis by using an adenoviral COX-2 overexpression system. In addition, we found that COX-2 regulates the transcription function of p53 as evidenced by suppression of p53 target gene induction by COX-2 cotransfection. Furthermore, COX-2 interacted with p53 in vitro and in vivo, which was inhibited by the treatment with NS-398. Taken together, these results suggest a novel function of COX-2 that inhibits DNA damage-induced apoptosis through direct regulation of p53 function.

PMID:
15707991
[PubMed - indexed for MEDLINE]
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