Establishment of an interactomic map of the Ets factors family: Towards a better understanding of their roles in oncogenic processes

Ets transcription factors have been involved in several cancers such as leukemia, prostate cancer
and Ewing’s sarcoma. They regulate the expression of genes controlling important biological
processes such as cellular proliferation, differentiation, apoptosis, metastasis, and transformation. This
family of transcription factors is characterized by its highly conserved DNA-binding domain called
the ETS domain and members are classified into subfamilies based on sequence homology criterion.
We built a protein-protein interaction (PPI) network of the 27 Ets proteins and of their individual
functional domains using a high-throughput yeast-two hybrid (Y2H) screening method. That Y2H
network was expanded with confident literature-curated PPIs to obtain a comprehensive Ets
interaction network. By considering connectivity between Ets interaction partners, we were able to
segregate highly connected clusters of proteins from that network. Analysis of ontologies
enrichment of those clusters enabled to confirm well-established roles and regulations of Ets factors,
but also to suggest new ones. Biological validation of one precise cluster could be used as a rule of
a thumb to globally confirm the bioinformatic analysis of our Ets PPI network and the potential
physiological or pathological roles and regulation of Ets factors.