EVI1 oncoprotein interacts with a large and complex network of proteins and integrates signals through protein phosphorylation

Significance Although ecotropic viral integration site 1 (EVI1) oncogenic transcription factor was discovered in 1988, its molecular functions and regulations are still underexplored. Through characterization of few EVI1-interacting proteins, EVI1 was identified as dynamic modulator of transcription and chromatin remodeling. We used proteomics approaches to define the EVI1 interactome. We found associations of EVI1 with not only transcriptional regulators, but also components of signaling pathways, DNA repair, DNA recombination, and mitosis complexes. We also identified functional EVI1 phosphorylation sites modified by casein-kinase II and protein phosphatase-1α that impact EVI1 activity. Thus, our study provides critical molecular insights on EVI1 action and regulation.