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PLoS One. 2013;8(2):e55883. doi: 10.1371/journal.pone.0055883. Epub 2013 Feb 6.

The level of Ets-1 protein is regulated by poly(ADP-ribose) polymerase-1 (PARP-1) in cancer cells to prevent DNA damage.

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1
CNRS USR 3078, Institut de Recherche Interdisciplinaire, Campus CNRS de la Haute Borne, Université Lille Nord de France, IFR 147, BP 70478, Villeneuve d'Ascq, France.

Abstract

Ets-1 is a transcription factor that regulates many genes involved in cancer progression and in tumour invasion. It is a poor prognostic marker for breast, lung, colorectal and ovary carcinomas. Here, we identified poly(ADP-ribose) polymerase-1 (PARP-1) as a novel interaction partner of Ets-1. We show that Ets-1 activates, by direct interaction, the catalytic activity of PARP-1 and is then poly(ADP-ribosyl)ated in a DNA-independent manner. The catalytic inhibition of PARP-1 enhanced Ets-1 transcriptional activity and caused its massive accumulation in cell nuclei. Ets-1 expression was correlated with an increase in DNA damage when PARP-1 was inhibited, leading to cancer cell death. Moreover, PARP-1 inhibitors caused only Ets-1-expressing cells to accumulate DNA damage. These results provide new insight into Ets-1 regulation in cancer cells and its link with DNA repair proteins. Furthermore, our findings suggest that PARP-1 inhibitors would be useful in a new therapeutic strategy that specifically targets Ets-1-expressing tumours.

PMID:
23405229
PMCID:
PMC3566071
DOI:
10.1371/journal.pone.0055883
[Indexed for MEDLINE]
Free PMC Article
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