Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast

SUBMITTER: Robert Liefke  

LAB HEAD: Robert Liefke

PROVIDER: PXD038414 | Pride | 2023-06-27

REPOSITORIES: Pride

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Action DRS
Evidence.txt Txt
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Ref2608_RL_01_20191031.raw Raw
Ref2608_RL_02_20191031.raw Raw
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Peptide-mediated inhibition of the transcriptional regulator Elongin BC induces apoptosis in cancer cells.

Fischer Sabrina S   Trinh Van Tuan VT   Simon Clara C   Weber Lisa M LM   Forné Ignasi I   Nist Andrea A   Bange Gert G   Abendroth Frank F   Stiewe Thorsten T   Steinchen Wieland W   Liefke Robert R   Vázquez Olalla O  

Cell chemical biology 20230623 7


Inhibition of protein-protein interactions (PPIs) via designed peptides is an effective strategy to perturb their biological functions. The Elongin BC heterodimer (ELOB/C) binds to a BC-box motif and is essential for cancer cell growth. Here, we report a peptide that mimics the high-affinity BC-box of the PRC2-associated protein EPOP. This peptide tightly binds to the ELOB/C dimer (k<sub>D</sub> = 0.46 ± 0.02 nM) and blocks the association of ELOB/C with its interaction partners, both in vitro a  ...[more]

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