E74-like factor 3 (ELF3)–Mediator complex subunit 23 (MED23) protein–protein interaction (ELF3–MED23 PPI)

The E74-like factor 3 (ELF3)–Mediator complex subunit 23 (MED23) protein–protein interaction is a critical regulatory node in the transcriptional control of genes involved in cell proliferation and oncogenesis. ELF3, an ETS-family transcription factor often referred to as ESX, is frequently overexpressed in epithelial-derived cancers, particularly HER2-positive breast cancer (Asano et al., 2002). It functions by recruiting the Mediator complex through a direct physical interaction with the MED23 subunit, which subsequently facilitates the assembly of the pre-initiation complex and RNA polymerase II recruitment (Stevens et al., 2002). This specific interaction is essential for the expression of the HER2 (ERBB2) gene itself, creating a positive feedback loop that drives tumor progression and therapeutic resistance (Sprouse et al., 2012). Disrupting this interaction with small-molecule inhibitors or peptidomimetics represents a promising therapeutic strategy to downregulate oncogenic signaling in aggressive cancers. Because this interaction is more specific than general transcriptional machinery, it offers a potential window for therapeutic intervention with reduced systemic toxicity compared to broad-spectrum transcriptional inhibitors. Research has identified experimental small molecules that mimic the ELF3 activation domain to block its binding to MED23, demonstrating efficacy in reducing tumor cell viability in vitro (Balamurugan et al., 2013). However, challenges remain regarding the potency and delivery of these protein-protein interaction inhibitors for clinical use.

Other names

ESX–Med23 interactionELF3–SUR2 interactionEpithelial-restricted with serine box–Mediator complex subunit 23 interactionE74-like factor 3–MED23 interaction

Inhibition of the physical interaction between the ELF3 activation domain and the MED23 subunit of the Mediator complex to prevent oncogenic gene transcription.