Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Eukaryotic Transcription Inhibitors

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Authentic Phosphorylation of α-Synuclein at Ser129 Reveals Functional Differences Not Captured by the S129D Phosphomimetic.

ACS chemical biology·2026

Same author

InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering.

ACS synthetic biology·2025

Same author

The syntenic long non-coding RNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene.

PLoS genetics·2025

Same author

Enhancing the Efficacy, Utility, and Throughput of the Transcription Block Survival Peptide Library Screening Platform.

JACS Au·2025

Same author

Stabilizing a Native Fold of Alpha-Synuclein with Short Helix-Constrained Peptides.

JACS Au·2025

Same author

Macrocyclic phage display for identification of selective protease substrates.

bioRxiv : the preprint server for biology·2025

Search research articles

Related Experiment Video

Updated: May 10, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

An Intracellular Peptide Library Screening Platform Identifies Irreversible Covalent Transcription Factor Inhibitors.

Andrew Brennan¹, Scott Lovell¹, Keith W Vance¹

¹Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|March 18, 2025

Summary

This summary is machine-generated.

Researchers developed a new screening platform to find covalent inhibitors of transcription factors (TFs). This method identified a potent peptide that irreversibly blocks the oncogenic TF cJun, inhibiting cancer cell viability.

Keywords:

activator protein‐1 cJun covalent inhibitor peptide antagonist protein–protein interactions transcription factor

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Experiment Videos

Last Updated: May 10, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Area of Science:

Molecular Biology
Drug Discovery
Chemical Biology

Background:

The Transcription Block Survival (TBS) assay was previously used to find reversible antagonists of the transcription factor (TF) cJun.
Existing methods lack the ability to identify covalent inhibitors and ensure high selectivity.

Purpose of the Study:

To expand the TBS methodology for identifying covalent and highly selective TF inhibitors.
To develop a peptide inhibitor targeting the oncogenic TF cJun with enhanced efficacy.

Main Methods:

Screening of a 131,072-member peptide library with cysteine options for disulfide bond formation.
Utilizing a non-reducing cell line to identify specific cysteine residues for covalent modification.
Substituting cysteine with an electrophile to create irreversible covalent inhibitors.

Main Results:

A single cysteine residue was identified for disulfide bond formation with cJun C269, leading to increased potency.
A selective covalent cJun inhibitor was generated, capable of penetrating melanoma cells and reducing oncogenic cJun levels.
The novel inhibitor demonstrated enhanced efficacy compared to previous cJun-targeting peptides.

Conclusions:

The enhanced covalent-TBS screening pipeline is a robust method for identifying ligandable cysteines on protein surfaces.
This approach yields potent, selective covalent antagonists with precisely positioned reactive groups.
The developed inhibitor effectively targets oncogenic cJun, inhibiting cell viability in melanoma models.