Open AccessThe Level of Ets-1 Protein Is Regulated by Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Cancer Cells to Prevent DNA Damage
Author(s) -
Arnaud J. Legrand,
Souhaila Choul-Li,
Corentin Spriet,
Thierry Idziorek,
Dorothée Vicogne,
Hervé Drobecq,
Françoise Dantzer,
Vincent Villeret,
Marc Aumercier
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0055883
Subject(s) - poly adp ribose polymerase , dna damage , dna repair , biology , cancer research , polymerase , parp inhibitor , cancer cell , microbiology and biotechnology , dna , cancer , genetics
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.