Study of the interaction between the oncoprotein Ets-1 and the enzyme PARP-1 : A new therapeutic approach in cancer ?

Arnaud Legrand
Institut de Recherche Interdisciplinaire

Ets-1 is a transcription factor of the Ets family. When overexpressed, it is involved in the development of invasive pathologies such as rheumatoid arthritis and cancers. Ets-1 regulates gene expression with partners by binding to specific DNA elements, called Ets binding sites (EBS), found in the promoters of its target genes. Therefore, the understanding of the specificity of its functions is linked to the characterization of its partners. For this purpose, we used an affinity purification strategy of Ets-1 partners using biotinylated Ets-1 for streptavidin pull-down. Several potential interaction partners were identified by MALDI-TOF mass spectrometry. Among those, we were able to identified, interacting with Ets-1, the Poly (ADP-Ribose) Polymerase-1 (PARP-1). PARP-1 is an abundant nuclear protein which catalyzes poly-ADP-ribosylation (PARylation) and plays diverse roles in many molecular and cellular processes, including DNA damage detection and repair and chromatin modification. Previous studies have revealed that besides its role in DNA repair pathway, PARP-1 is involved in the regulation of different transcription factors. In this study, we show that Ets-1 interacts directly with PARP-1. Using PARP-1 catalytic inhibitors, our results show that parylation of Ets-1 has direct consequences on its activity. Taken together, these findings strengthen the idea of a functional link between transcription factors and DNA repair proteins. Furthermore, inhibition of PARP-1 could be a new strategy to target Ets-1 activity in tumours.