New functions of the oncoprotein Ets-1

Ets-1 is the founding member of the family of transcription factors Ets. Ets-1 is mainly expressed in embryonic tissues. The pathological expression of Ets-1 is partly responsible for the proliferation and invasion abilities of tumor cells. Therefore, Ets-1 is currently considered as a marker of poor prognosis in several cancers. We recently demonstrated that Ets-1 interacts with enzymes involved in DNA repair and chromatin remodeling. The nature of these new partners strongly suggests new Ets-1 functions that have not been considered yet. Why Ets-1, a transcription factor recognized for its role in tumor progression, establishes interactions with DNA repair enzymes ? This discovery questions the role of Ets-1 as a pure transcription factor and suggests that it can also be involved in DNA repair and other “cryptic” functions. Using the interdisciplinary approaches of molecular systems biology we aim to decipher the new functions of Ets-1. We want to i) characterize the new partners of Ets-1 that we have identified and validated in the tumor progression context ; ii) study the interaction between Ets-1 and these new partners using functional and structural approaches and iii) alter the interactions between Ets-1 and its new partners in order to evaluate their impact on the cancer cell phenotype.