ETS proto-oncogene 1 (ETS1)

ETS proto-oncogene 1 (ETS1) is a founding member of the ETS family of transcription factors, characterized by a highly conserved winged helix-turn-helix DNA-binding domain [UniProt: P14921]. It acts as a critical nuclear integrator of the MAPK/ERK signaling pathway, regulating genes essential for cell proliferation, survival, and tissue remodeling [PMID: 25613340]. In oncology, ETS1 is frequently overexpressed and serves as a driver of tumor progression, promoting angiogenesis and the epithelial-mesenchymal transition (EMT) which facilitates metastasis [PMID: 15507677]. Beyond its role in cancer, ETS1 is a master regulator of immune cell development, particularly for T-cells and B-cells; consequently, its dysregulation is strongly linked to autoimmune pathologies such as systemic lupus erythematosus [PMID: 30108119]. While direct therapeutic targeting of ETS1 is challenging due to its nature as a transcription factor, current research focuses on small molecules that disrupt its DNA-binding interface or its interactions with transcriptional co-activators [PMID: 28655779].

Other names

Protein C-ets-1p54EWSR2ETS-1v-ets erythroblastosis virus E26 oncogene homolog 1

Inhibition of the ETS1 DNA-binding domain to prevent transcriptional activation of target genes, or indirect modulation via the inhibition of upstream MAPK/ERK signaling pathways that regulate ETS1 phosphorylation and activity [PMID: 28655779, PMID: 24639177].