Peptide-mediated inhibition of the transcriptional regulator Elongin BC induces apoptosis in cancer cells

Inhibiting protein-protein interactions via designed peptides is a suitable strategy to block the function of important proteins in cells. The Elongin BC heterodimer (ELOB/C) is involved in transcription elongation and protein turnover. It interacts with target proteins via a so-called BC-box to modulate their functions. ELOB and ELOC are commonly upregulated in cancer and are essential for cancer cell growth, making them attractive drug targets. However, currently, no strategy has been established to inhibit the function of ELOB/C in cells. Here, we show that peptides that mimic the high-affinity BC-box of EPOP can block the interaction of ELOB/C with its target proteins, both in vitro and in the cellular environment. Cancer cells treated with BC-box peptides, but not with the mutated control, show decreased cell viability, altered cell cycle and increased apoptosis, demonstrating a biological impact by inhibiting ELOB/C in vivo. Together our work suggests that targeting the BC-box binding pocket of ELOB/C is a feasible strategy to impair the function of the ELOB/C heterodimer and to inhibit cancer cell growth.