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Updated: Jan 16, 2026
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Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
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Gαq-Stimulated Gene Expression Is Insensitive to Bromo Extra Terminal Domain Inhibitors in HEK 293 Cells.
Ashika Jain1, Viviane Pagé1, Dominic Devost1
1Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
International Journal of Molecular Sciences
|September 27, 2025
Summary
Bromodomain and extraterminal domain (BET) proteins like Brd4 are crucial for cell functions. This study reveals Brd4
Area of Science:
- Molecular Biology
- Cellular Signaling
- Pharmacology
Background:
- Bromodomain and extraterminal domain (BET) proteins are transcriptional co-activators involved in cell differentiation, proliferation, and stress responses.
- Pharmacological inhibition of BET proteins shows therapeutic potential for pathological gene expression.
- Cell-type and signaling pathway specific requirements for BET protein dependence are not fully understood.
Purpose of the Study:
- To investigate the differential responsiveness of the BET protein Brd4 to G protein alpha subunits (Gαs and Gαq) in HEK 293 cells.
- To compare Brd4 responsiveness to G protein signaling in HEK 293 cells with previous findings in neonatal rat cardiomyocytes.
Main Methods:
- Utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to express Gαs- or Gαq-coupled receptors in HEK 293 cells.
- Administered pharmacological BET inhibitors (JQ1 and dBET6) to assess their impact on gene expression.
- Analyzed gene expression changes induced by G protein signaling and BET inhibition.
Main Results:
- Gαq signaling induced early response and inflammatory genes largely independent of BET inhibition.
- Gαs signaling activated a subset of Gαq-induced genes, an effect significantly reversed by the BET degrader dBET6.
- Findings in HEK 293 cells are consistent with previous observations in cardiomyocytes regarding Gαq-induced BET-insensitive gene expression.
Conclusions:
- Brd4 responsiveness to G protein signaling is isoform-specific, with Gαq-mediated responses being largely BET-insensitive.
- Gαs-mediated gene expression shows a greater dependence on BET proteins, particularly Brd4.
- Suggests potential general signaling requirements for activating Brd4 across different cell types.
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