title: The level of Ets-1 protein is regulated by poly(ADP-ribose) polymerase-1 (PARP-1) in cancer cells to prevent DNA damage.
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.
authors: 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.
authors: Arnaud J
authors: AJ
authors: Legrand
authors: Souhaila
authors: S
authors: Choul-Li
authors: Corentin
authors: C
authors: Spriet
authors: Thierry
authors: T
authors: Idziorek
authors: Dorothée
authors: D
authors: Vicogne
authors: Hervé
authors: H
authors: Drobecq
authors: Françoise
authors: F
authors: Dantzer
authors: Vincent
authors: V
authors: Villeret
authors: Marc
authors: M
authors: Aumercier
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic
chemical_list: C494041:ETS1 protein, human; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases